48 results on '"La Manna, Marco Pio"'
Search Results
2. Role of hematopoietic cells in Mycobacterium tuberculosis infection
- Author
-
Tamburini, Bartolo, Badami, Giusto Davide, Azgomi, Mojtaba Shekarkar, Dieli, Francesco, La Manna, Marco Pio, and Caccamo, Nadia
- Published
- 2021
- Full Text
- View/download PDF
3. Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data Reveals Memory-like NK Cell Subset Associated with Mycobacterium tuberculosis Latency.
- Author
-
Shekarkar Azgomi, Mojtaba, Badami, Giusto Davide, Lo Pizzo, Marianna, Tamburini, Bartolo, Dieli, Costanza, La Manna, Marco Pio, Dieli, Francesco, and Caccamo, Nadia
- Subjects
MYCOBACTERIUM tuberculosis ,KILLER cells ,RNA sequencing ,NUCLEOTIDE sequence ,INNATE lymphoid cells ,LATENT tuberculosis - Abstract
Natural killer (NK) cells are innate-like lymphocytes that belong to the family of type-1 innate lymphoid cells and rapidly respond to virus-infected and tumor cells. In this study, we have combined scRNA-seq data and bulk RNA-seq data to define the phenotypic and molecular characteristics of peripheral blood NK cells. While the role of NK cells in immune surveillance against virus infections and tumors has been well established, their contribution to protective responses to other intracellular microorganisms, such as Mycobacterium tuberculosis (Mtb), is still poorly understood. In this study, we have combined scRNA-seq data and bulk RNA-seq data to illuminate the molecular characteristics of circulating NK cells in patients with active tuberculosis (TB) disease and subjects with latent Mtb infection (LTBI) and compared these characteristics with those of healthy donors (HDs) and patients with non-TB other pulmonary infectious diseases (ODs). We show here that the NK cell cluster was significantly increased in LTBI subjects, as compared to patients with active TB or other non-TB pulmonary diseases and HD, and this was mostly attributable to the expansion of an NK cell population expressing KLRC2, CD52, CCL5 and HLA-DRB1, which most likely corresponds to memory-like NK2.1 cells. These data were validated by flow cytometry analysis in a small cohort of samples, showing that LTBI subjects have a significant expansion of NK cells characterized by the prevalence of memory-like CD52
+ NKG2C+ NK cells. Altogether, our results provide some new information on the role of NK cells in protective immune responses to Mtb. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
4. Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer's Disease.
- Author
-
Tamburini, Bartolo, Badami, Giusto Davide, La Manna, Marco Pio, Shekarkar Azgomi, Mojtaba, Caccamo, Nadia, and Dieli, Francesco
- Subjects
ALZHEIMER'S disease ,NATURAL immunity ,INFLAMMATION ,AMYLOID plaque ,TAU proteins ,CEREBROSPINAL fluid - Abstract
The inflammatory response that marks Alzheimer's disease (neuroinflammation) is considered a double-edged sword. Microglia have been shown to play a protective role at the beginning of the disease. Still, persistent harmful stimuli further activate microglia, inducing an exacerbating inflammatory process which impairs β-amyloid peptide clearance capability and leads to neurotoxicity and neurodegeneration. Moreover, microglia also appear to be closely involved in the spread of tau pathology. Soluble TREM2 also represents a crucial player in the neuroinflammatory processes. Elevated levels of TREM2 in cerebrospinal fluid have been associated with increased amyloid plaque burden, neurodegeneration, and cognitive decline in individuals with Alzheimer's disease. Understanding the intricate relationship between innate immunity and Alzheimer's disease will be a promising strategy for future advancements in diagnosis and new therapeutic interventions targeting innate immunity, by modulating its activity. Still, additional and more robust studies are needed to translate these findings into effective treatments. In this review, we focus on the role of cells (microglia, astrocytes, and oligodendrocytes) and molecules (TREM2, tau, and β-amyloid) of the innate immune system in the pathogenesis of Alzheimer's disease and their possible exploitation as disease biomarkers and targets of therapeutical approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
5. B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma.
- Author
-
Mohammadnezhad, Leila, Shekarkar Azgomi, Mojtaba, La Manna, Marco Pio, Guggino, Giuliana, Botta, Cirino, Dieli, Francesco, and Caccamo, Nadia
- Subjects
DIFFUSE large B-cell lymphomas ,SJOGREN'S syndrome ,B cell receptors ,NON-Hodgkin's lymphoma ,AUTOIMMUNE diseases ,CELL communication - Abstract
Primary Sjogren syndrome (pSS) is the second most common autoimmune disorder worldwide, which, in the worst scenario, progresses to Non-Hodgkin Lymphoma (NHL). Despite extensive studies, there is still a lack of knowledge about developing pSS for NHL. This study focused on cells' signaling in pSS progression to the NHL type of diffuse large B-cell lymphoma (DLBCL). Using bulk RNA and single cell analysis, we found five novel pathologic-independent clusters in DLBCL based on cells' signaling. B-cell receptor (BCR) signaling was identified as the only enriched signal in DLBCL and pSS peripheral naive B-cells or salivary gland-infiltrated cells. The evaluation of the genes in association with BCR has revealed that targeting CD79A, CD79B, and LAMTOR4 as the shared genes can provide novel biomarkers for pSS progression into lymphoma. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. Downregulation of miRNA17–92 cluster marks Vγ9Vδ2 T cells from patients with rheumatoid arthritis
- Author
-
Guggino, Giuliana, Orlando, Valentina, Saieva, Laura, Ruscitti, Piero, Cipriani, Paola, La Manna, Marco Pio, Giacomelli, Roberto, Alessandro, Riccardo, Triolo, Giovanni, Ciccia, Francesco, Dieli, Francesco, and Caccamo, Nadia
- Published
- 2018
- Full Text
- View/download PDF
7. Reversible Effect of Magnetic Fields on Human Lymphocyte Activation Patterns: Different Sensitivity of Naive and Memory Lymphocyte Subsets
- Author
-
Salerno, Sergio, La Mendola, Carmela, La Manna, Marco Pio, Casto, Antonio Lo, Caccamo, Nadia, and Salerno, Alfredo
- Published
- 2009
- Full Text
- View/download PDF
8. Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis
- Author
-
Ciccia, Francesco, Guggino, Giuliana, Rizzo, Aroldo, Manzo, Antonio, Vitolo, Barbara, La Manna, Marco Pio, Giardina, Giuseppina, Sireci, Guido, Dieli, Francesco, Montecucco, Carlo Maurizio, Alessandro, Riccardo, and Triolo, Giovanni
- Published
- 2015
- Full Text
- View/download PDF
9. The Abundance of Tumor-Infiltrating CD8 + Tissue Resident Memory T Lymphocytes Correlates with Patient Survival in Glioblastoma.
- Author
-
La Manna, Marco Pio, Di Liberto, Diana, Lo Pizzo, Marianna, Mohammadnezhad, Leila, Shekarkar Azgomi, Mojtaba, Salamone, Vincenzo, Cancila, Valeria, Vacca, Davide, Dieli, Costanza, Maugeri, Rosario, Brunasso, Lara, Iacopino, Domenico Gerardo, Dieli, Francesco, and Caccamo, Nadia
- Subjects
T cells ,OVERALL survival ,GLIOBLASTOMA multiforme ,CD8 antigen ,LYMPHOCYTE subsets - Abstract
Glial tumors alone account for 40% of all CNS tumors and present a low survival rate. The tumor microenvironment is a critical regulator of tumor progression and therapeutic effectiveness in glioma. Growing evidence from numerous studies of human solid tumor-infiltrating CD8
+ T cells indicates that tissue-resident memory T cells (TRM) represent a substantial subpopulation of tumor-infiltrating lymphocytes (TILs). Although it is reported that some types of cancer patients with high immune infiltration tend to have better outcomes than patients with low immune infiltration, it seems this does not happen in gliomas. This study aimed to characterize TRMs cells in the glioma tumor microenvironment to identify their potential predictive and prognostic role and the possible therapeutic applications. Fluorescence activated cell sorting (FACS) analysis and immunofluorescence staining highlighted a statistically significant increase in CD8+ TRM cells (CD103+ and CD69+ CD8+ T cells) in gliomas compared to control samples (meningioma). In-silico analysis of a dataset of n = 153 stage IV glioma patients confirmed our data. Moreover, the gene expression analysis showed an increase in the expression of TRM-related genes in tumor tissues compared to normal tissues. This analysis also highlighted the positive correlation between genes associated with CD8+ TRM and TILs, indicating that CD8+ TRMs cells are present among the infiltrating T cells. Finally, high expression of Integrin subunit alpha E (ITGAE), the gene coding for the integrin CD103, and high CD8+ TILs abundance were associated with more prolonged survival, whereas high ITGAE expression but low CD8+ TILs abundance were associated with lower survival. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
10. Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells.
- Author
-
La Manna, Marco Pio, Shekarkar Azgomi, Mojtaba, Tamburini, Bartolo, Badami, Giusto Davide, Mohammadnezhad, Leila, Dieli, Francesco, and Caccamo, Nadia
- Subjects
IMMUNOLOGIC memory ,STEM cells ,IMMUNE response ,MEMORY ,PHENOTYPES - Abstract
The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases. Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as "memory". T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we examine recent developments in the characterization of the heterogeneity of the memory T cell compartment. In particular, we focus on the emerging role of CD8
+ TRM and TSCM cells, providing evidence on how their immunometabolism or modulation can play a vital role in their generation and maintenance in chronic conditions such as infections or autoimmune diseases. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
11. Metabolic Reprogramming of Innate Immune Cells as a Possible Source of New Therapeutic Approaches in Autoimmunity.
- Author
-
Mohammadnezhad, Leila, Shekarkar Azgomi, Mojtaba, La Manna, Marco Pio, Sireci, Guido, Rizzo, Chiara, Badami, Giusto Davide, Tamburini, Bartolo, Dieli, Francesco, Guggino, Giuliana, and Caccamo, Nadia
- Subjects
THERAPEUTICS ,AUTOIMMUNITY ,NATURAL immunity ,AUTOIMMUNE diseases ,CELL differentiation - Abstract
Immune cells undergo different metabolic pathways or immunometabolisms to interact with various antigens. Immunometabolism links immunological and metabolic processes and is critical for innate and adaptive immunity. Although metabolic reprogramming is necessary for cell differentiation and proliferation, it may mediate the imbalance of immune homeostasis, leading to the pathogenesis and development of some diseases, such as autoimmune diseases. Here, we discuss the effects of metabolic changes in autoimmune diseases, exerted by the leading actors of innate immunity, and their role in autoimmunity pathogenesis, suggesting many immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Correction: Shekarkar Azgomi et al. A Rapid and Simple Multiparameter Assay to Quantify Spike-Specific CD4 and CD8 T Cells after SARS-CoV-2 Vaccination: A Preliminary Report. Biomedicines 2021, 9 , 1576.
- Author
-
Shekarkar Azgomi, Mojtaba, La Manna, Marco Pio, Badami, Giusto Davide, Ragonese, Paolo, Trizzino, Antonino, Dieli, Francesco, and Caccamo, Nadia
- Subjects
T cells ,CD8 antigen ,CD4 antigen ,SARS-CoV-2 ,VACCINATION - Abstract
Analysis of distinct cytokine expression by spike-specific CD4+ (C) and CD8+ (D) T cells using a Kruskal-Wallis test with Dunn's correction. A Rapid and Simple Multiparameter Assay to Quantify Spike-Specific CD4 and CD8 T Cells after SARS-CoV-2 Vaccination: A Preliminary Report. Gating strategy used to identify spike-specific CD4+ and CD8+ T cells and to detect their cytokine expression in response to spike-derived peptides. [Extracted from the article]
- Published
- 2023
- Full Text
- View/download PDF
13. HLA-E–restricted CD8+ T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Coinfection.
- Author
-
La Manna, Marco Pio, Orlando, Valentina, Prezzemolo, Teresa, Carlo, Paola Di, Cascio, Antonio, Delogu, Giovanni, Poli, Guido, Sullivan, Lucy C., Brooks, Andrew G., Dieli, Francesco, and Caccamo, Nadia
- Subjects
HLA histocompatibility antigens ,CD8 antigen ,MYCOBACTERIUM tuberculosis ,HIV infections ,TETRAMERS (Oligomers) - Abstract
We investigated the contribution of human leukocyte antigen A2 (HLA-A2) and HLA-E–restricted CD8
+ T cells in patients with Mycobacterium tuberculosis and human immunodeficiency virus 1 (HIV-1) coinfection. HIV-1 downregulates HLA-A, -B, and -C molecules in infected cells, thus influencing recognition by HLA class I–restricted CD8+ T cells but not by HLA-E–restricted CD8+ T cells, owing to the inability of the virus to downmodulate their expression. Therefore, antigen-specific HLA-E–restricted CD8+ T cells could play a protective role in Mycobacterium tuberculosis and HIV-1 coinfection. HLA-E– and HLA-A2–restricted Mycobacterium tuberculosis–specific CD8+ T cells were tested in vitro for cytotoxic and microbicidal activities, and their frequencies and phenotypes were evaluated ex vivo in patients with active tuberculosis and concomitant HIV-1 infection. HIV-1 and Mycobacterium tuberculosis coinfection caused downmodulation of HLA-A2 expression in human monocyte–derived macrophages associated with resistance to lysis by HLA-A2–restricted CD8+ T cells and failure to restrict the growth of intracellular Mycobacterium tuberculosis. Conversely, HLA-E surface expression and HLA-E–restricted cytolytic and microbicidal CD8 responses were not affected. HLA-E–restricted and Mycobacterium tuberculosis–specific CD8+ T cells were expanded in the circulation of patients with Mycobacterium tuberculosis/HIV-1 coinfection, as measured by tetramer staining, but displayed a terminally differentiated and exhausted phenotype that was rescued in vitro by anti–PD-1 (programmed cell death protein 1) monoclonal antibody. Together, these results indicate that HLA-E–restricted and Mycobacterium tuberculosis–specific CD8+ T cells in patients with Mycobacterium tuberculosis/HIV-1 coinfection have an exhausted phenotype and fail to expand in vitro in response to antigen stimulation, which can be restored by blocking the PD-1 pathway using the specific monoclonal antibody nivolumab. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
14. Mycobacterium tuberculosis Drives Expansion of Low-Density Neutrophils Equipped With Regulatory Activities.
- Author
-
La Manna, Marco Pio, Orlando, Valentina, Paraboschi, Elvezia Maria, Tamburini, Bartolo, Di Carlo, Paola, Cascio, Antonio, Asselta, Rosanna, Dieli, Francesco, and Caccamo, Nadia
- Subjects
MYCOBACTERIUM tuberculosis ,NEUTROPHILS ,TUBERCULOSIS ,SUPPRESSOR cells ,PATHOLOGY - Abstract
In human tuberculosis (TB) neutrophils represent the most commonly infected phagocyte but their role in protection and pathology is highly contradictory. Moreover, a subset of low-density neutrophils (LDNs) has been identified in TB, but their functions remain unclear. Here, we have analyzed total neutrophils and their low-density and normal-density (NDNs) subsets in patients with active TB disease, in terms of frequency, phenotype, functional features, and gene expression signature. Full-blood counts from Healthy Donors (H.D.), Latent TB infected, active TB, and cured TB patients were performed. Frequency, phenotype, burst activity, and suppressor T cell activity of the two different subsets were assessed by flow cytometry while NETosis and phagocytosis were evaluated by confocal microscopy. Expression analysis was performed by using the semi-quantitative RT-PCR array technology. Elevated numbers of total neutrophils and a high neutrophil/lymphocyte ratio distinguished patients with active TB from all the other groups. PBMCs of patients with active TB disease contained elevated percentages of LDNs compared with those of H.D., with an increased expression of CD66b, CD33, CD15, and CD16 compared to NDNs. Transcriptomic analysis of LDNs and NDNs purified from the peripheral blood of TB patients identified 12 genes differentially expressed: CCL5, CCR5, CD4, IL10, LYZ , and STAT4 were upregulated, while CXCL8, IFNAR1, NFKB1A, STAT1, TICAM1 , and TNF were downregulated in LDNs, as compared to NDNs. Differently than NDNs, LDNs failed to phagocyte live Mycobacterium tuberculosis (M. tuberculosis) bacilli, to make oxidative burst and NETosis, but caused significant suppression of antigen-specific and polyclonal T cell proliferation which was partially mediated by IL-10. These insights add a little dowel of knowledge in understanding the pathogenesis of human TB. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
15. MONOCYTES MACROPHAGES EXPRESSION OF Ml OR M2 PHENOTYPES IN LATENT TUBERCULOSIS, ACTIVE DISEASES AND UNINFECTED MIGRANTS AND SICILIAN PATIENTS
- Author
-
La Manna, Marco Pio, Paola Di Carlo, Claudia Colomba, Tumminia, S., Pasquale, Q., Carmela, Z., Adriana, C., Alice, M., Mililli, D., Guadagnino, G., Antonio Cascio, Caccamo, Nadia Rosalia, LA MANNA, M., DI CARLO, P., Colomba, C., Tumminia, S., Pasquale, Q., Carmela, Z., Adriana, C., Alice, M., Mililli, D., Guadagnino, G., Cascio, A., and Caccamo, N.
- Subjects
MONOCYTES, Ml OR M2 PHENOTYPES, TUBERCULOSIS - Abstract
The high grade ofphenotype plasticity of monocytes macrophages, is resumed in two different cell subsets named M1 or M2. Several studies of microbial infections in vitro and in vivo, showed that, during the early stage of infection, macrophages are polarized toward Ml phenotype that should be protective against pathogen, while during the chronic phase of infection/disease macrophages polarize toward M2 phenotype to avoid damages from a prolonged Ml type activation.Obiettivo: In order to investigate if Mycobacterium tuberculosis infection can drive circulating monocytes toward the expression of Ml or M2 phenotypes, we have analyzed by flow cytometry monocytes obtained from patients with active tuberculosis (TB) at early phase of disease and during anti mycobacterial therapy, subjects with latent TB and healthy uninfected control. Risultatil Analysis of surface markers expression showed no clearcut Ml/M2 polarization in all tested groups, but we found a very high percentage of RANK+ monocytes in patients with active TB disease before treatment, while RANK expression was very faint in monocytes from all other experimental groups. Moreover the statistical analysis of geometric MFI of RANK showed a signifìcant difference between patients with active disease compared to all the others groups. Conclusioni: Given that the available in vitro diagnostic tests are limited in discriminating subjects with latent or active disease, as well as response to therapy,,we speculate that the evaluation of RANK expression on monocytes could represent an additional biomarker useful to support diagnosis of active disease and monitor the response to therapy.
- Published
- 2016
16. Evaluation of Bone Marrow CD8+ tissue-Resident Memory T Cells in Multiple Myeloma
- Author
-
Carlisi, Melania, Mancuso, Salvatrice, La Manna, Marco Pio, Orlando, Valentina, Caccamo, Nadia, and Siragusa, Sergio
- Published
- 2019
- Full Text
- View/download PDF
17. Preliminary results of EOLIFE99, a project concerning the conservation of four endangered plant species of Aeolian Archipelago (South Tyrrhenian Sea, Italy)
- Author
-
TROIA, Angelo, CARDINALE, Massimiliano, LA MANNA, Marco Pio, PUGLIA, Anna Maria, QUATRINI, Paola, LO CASCIO P, PASTA S, VOUTSINAS E., Troia, Angelo, Cardinale, Massimiliano, La Manna, Marco Pio, Lo Cascio, Pietro, Pasta, Salvatore, Puglia, Anna Maria, Quatrini, Paola, Voutsinas, Emanuela, TROIA A, CARDINALE M, LA MANNA M, LO CASCIO P, PASTA S, PUGLIA AM, QUATRINI P, and VOUTSINAS E
- Subjects
con ervation, endangered plants, Aeolian Islands - Published
- 2005
18. Heterogeneity and prognostic influence of tumor-infiltrating gamma-delta T lymphocytes in colon cancer patients
- Author
-
Dieli Francesco, Caccamo Nadia, Cutrera Stella, Di Liberto Diana, La Manna Marco Pio, Buccheri Simona, Orlando Valentina, Cicero Giuseppe, Meraviglia Serena, Lo Presti Elena, Lo Presti, E, Meraviglia, S, Cicero, G, Orlando, V, Buccheri, S, La Manna, MP, Di Liberto, D, Cutrera, S, Caccamo, N, and Dieli, F
- Subjects
gamma-delta T cells, Colon Cancer, immunosurveillance, Immunotherapy, tumor immunity ,business.industry ,Colorectal cancer ,Immunology ,Cancer research ,Medicine ,Immunology and Allergy ,business ,medicine.disease - Published
- 2013
- Full Text
- View/download PDF
19. Identification of plasma biomarkers for discrimination between tuberculosis infection/disease and pulmonary non tuberculosis disease.
- Author
-
La Manna, Marco Pio, Orlando, Valentina, Li Donni, Paolo, Sireci, Guido, Di Carlo, Paola, Cascio, Antonio, Dieli, Francesco, and Caccamo, Nadia
- Subjects
- *
TUBERCULOSIS , *BLOOD plasma , *INTERFERON gamma release tests , *BLOOD cells , *CHEMOKINES - Abstract
We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon γ Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells. The diagnostic accuracies of the markers detected were evaluated by ROC curve analysis and by the combination of multiple biomarkers to improve the potential to discriminate between infection/disease and non infection. Among 48 cytokines, 13 analytes, namely IL-3, IL-12-p40, LIF, IFNα2, IL-2ra, IL-13, b-NGF, SCF, TNF-β, TRAIL, IL-2, IFN-γ, IP-10, and MIG, were significantly higher in the active TB and LTBI groups, compared to NON-TB patients, while MIF was significantly lower in active TB patients compared to NON-TB and LTBI groups. The diagnostic accuracies of the markers detected in the culture supernatants evaluated by ROC curve analysis revealed that 11 analytes (IL2, IP10, IFN-γ, IL13, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2 Ra, LIF) discriminated between NON-TB and LTBI groups, with AUC for all analytes ≥0.73, while 14 analytes (IL2, IP10, IFN-γ, MIG, SCF, b-NGF, IL12-p40, TRAIL, IL2Ra, MIF, TNF-β, IL3, IFN-α2, LIF) discriminated between NON-TB and active TB groups, with AUC ≥0.78, that is a moderate, value in terms of accuracy of a diagnostic test. Finally, the combinations of seven biomarkers resulted in the accurate prediction of 88.89% of active TB patients, 82.35% of subjects with latent infection and 90% of non-TB patients, respectively. Taken together, our data suggest that combinations of whole blood Mycobacterium tuberculosis (Mtb) antigen dependent cytokines production could be useful as biomarkers to determine tuberculosis disease states when compared to non TB cohort. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
20. The Janus Face of NKT Cell Function in Autoimmunity and Infectious Diseases.
- Author
-
Torina, Alessandra, Guggino, Giuliana, La Manna, Marco Pio, and Sireci, Guido
- Subjects
KILLER cells ,T cells ,AUTOIMMUNITY ,SULFATIDES ,GLYCOLIPIDS ,ENDOPLASMIC reticulum - Abstract
Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II, and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defense against infections but, on the other hand, their effector functions can be involved in the pathogenesis of several inflammatory disorders due to their exposure to different microbial or self-antigens, respectively. A deep understanding of the biology and functions of type I, II, and NKT-like cells as well as their interplay with cell types acting in innate (neuthrophils, innate lymphoid cells, machrophages, and dendritic cells) and adaptive immunity (CD4
+ ,CD8+ , and double negative T cells) should be important to design potential immunotherapies for infectious and autoimmune diseases. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
21. Antigen-Specific T Cells and Cytokines Detection as Useful Tool for Understanding Immunity against Zoonotic Infections
- Author
-
Agnone, Annalisa, Torina, Alessandra, Vesco, Gesualdo, Villari, Sara, Vitale, Fabrizio, Caracappa, Santo, La Manna, Marco Pio, Dieli, Francesco, and Sireci, Guido
- Subjects
Article Subject - Abstract
Zoonoses include a broad range of diseases, that are becoming of great interest, due to the climate changing, that cause the adaptation of vectors to new niches and environments. Host immune responses play a crucial role in determining the outcome of infections, as documented by expansion of antigen-specific T cells during several zoonotic infections. Thus, understanding of the contribution of antigen-specific T-cell subsets in the host immune response is a powerful tool to evaluate the different immunological mechanisms involved in zoonotic infections and for the development of effective vaccines. In this paper we discuss the role of T cells in some eukaryotic and prokaryotic infectious models.
- Published
- 2012
- Full Text
- View/download PDF
22. New insight on immunological activation pathways of Langerhans cells, possible tolerogenic role
- Author
-
LA MANNA, Marco Pio, BAZAN, Viviana, GERBINO, Aldo, SALERNO, Alfredo, Gerbino, A, Zummo, G, Crescimanno, G, La Manna, M, Bazan, V, and Salerno, A
- Subjects
Langerhans cells, Role Tolerogenic - Abstract
Langerhans cells are the prototype of antigen presenting cell, their role is to work as sentinel in the epidermis. Like every APC Langerhans cells act as bridge between innate and acquired immunity recognizing antigens into the epidermis and bringing them to drying lymph node, their work is well described by the Langerhans cell paradigm. Recently many works designed a new and amazing role of Langerhans cells in fact they often showed tolerogenic capacity, while in many cases, they seems not necessary to promote activation of acquired immunity. Anyway Langerhans cells remaining an interesting target for new vaccine strategies because of their localization in the epidermis and the ability to capture antigens trough different recognition pathways. Also interesting is the possible use of langerhans cells for their tolerogenic capacity, in many experimental models these cells opportunely addressed with appropriated cytokines appears able to down-regulate immune system response in autoimmune pathology.
- Published
- 2009
23. In Naive mice in vivo localization of WI specific CD8+CD28- induced cells
- Author
-
MACALUSO, Pasquale, BUSCEMI, Maria, SPATOLA, Giovanni Francesco, UZZO, Maria Laura, LA MANNA, Marco Pio, SIRECI, Guido, SALERNO, Alfredo, GERBINO, Aldo, Macaluso,P, Buscemi,M, Spatola,GF, Uzzo,ML, La Manna,MP, Sireci,G, Salerno,A, and Gerbino,A
- Subjects
CD8+CD28 ,Settore BIO/17 - Istologia ,Settore MED/04 - Patologia Generale - Published
- 2008
24. EFFECTS OF ELECTROMAGNETIC FIELDS ON IFN-GAMMA RELEASE AND CONTENENT FROM HUMAN SUBSETS OF CD4+T CELLS
- Author
-
LA MENDOLA, Carmela, LO CASTO, Antonio, CACCAMO, Nadia Rosalia, SALERNO, Sergio, LA MANNA, Marco Pio, BRAI, Maria, LAGALLA, Roberto, M. Pio, C La Mendola, A Lo Casto, N Caccamo, S Salerno, M Pio, MP La Manna, M Brai, and R Lagalla
- Subjects
EFFECTS OF ELECTROMAGNETIC FIELDS, CD4+T CELLS - Published
- 2008
25. Quantitative and qualitative profiles of circulating monocytes may help identifying tuberculosis infection and disease stages.
- Author
-
La Manna, Marco Pio, Orlando, Valentina, Dieli, Francesco, Di Carlo, Paola, Cascio, Antonio, Cuzzi, Gilda, Palmieri, Fabrizio, Goletti, Delia, and Caccamo, Nadia
- Subjects
- *
TUBERCULOSIS -- Immunological aspects , *TUBERCULOSIS risk factors , *MONOCYTES , *LYMPHOCYTES , *MORTALITY , *DISEASE progression - Abstract
Tuberculosis (TB) is one of the most important cause of morbidity and death among infectious diseases, and continuous efforts are needed to improve diagnostic tools and therapy. Previous published studies showed that the absolute cells number of monocytes or lymphocytes in peripheral blood or yet the ratio of monocytes to lymphocytes displayed the ability to predict the risk of active TB. In the present study we evaluated the ratio of monocytes to lymphocytes variation and we also analyzed the ex-vivo expression of CD64 on monocytes as tools to identify biomarkers for discriminating TB stages. Significant differences were found when the average ratio of monocytes to lymphocytes of active TB patients was compared with latent TB infection (LTBI) subjects, cured TB and healthy donors (HD). By the receiver operator characteristics (ROC) curve analysis the cut-off value of 0.285, allowed the discrimination of active TB from HD, with a sensitivity of 91.04% and a specificity of 93.55% (95% of confidence interval: 0.92–0.99). The ROC curve analysis comparing TB patients and LTBI groups, led to a sensitivity and the specificity of the assay of 85.07% and 85.71%, respectively (95% of confidence interval: 0.85 to 0.96). The upregulation of CD64 expression on circulating monocytes in active TB patients could represent an additional biomarker for diagnosis of active TB. In conclusion, we found that the ML ratio or monocyte absolute count or phenotypic measures show predictive value for active TB. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
26. Functional signatures of human CD4 and CD8T cell responses to Mycobacterium tuberculosis.
- Author
-
Prezzemolo, Teresa, Guggino, Giuliana, La Manna, Marco Pio, Di Liberto, Diana, Dieli, Francesco, and Caccamo, Nadia
- Subjects
CD4 antigen ,MYCOBACTERIUM tuberculosis ,COMMUNICABLE diseases ,DRUG resistance ,CYTOKINES ,T cells ,IMMUNODEFICIENCY - Abstract
With 1.4 million deaths and 8.7 million new cases in 2011, tuberculosis (TB) remains a global health care problem and together with HIV and Malaria represents one of the three infectious diseases world-wide. Control of the global TB epidemic has been impaired by the lack of an effective vaccine, by the emergence of drug-resistant forms of Mycobacterium tuberculosis (Mtb) and by the lack of sensitive and rapid diagnostics. It is estimated, by epidemiological reports, that one third of the world's population is latently infected with Mtb, but the majority of infected individuals develop long-lived protective immunity, which controls and contains Mtb in a T cell-dependent manner. Development of TB disease results from interactions among the environment, the host, and the pathogen, and known risk factors include HIV co-infection, immunodeficiency, diabetes mellitus, overcrowding, malnutrition, and general poverty; therefore, an effective T cell response determines whether the infection resolves or develops into clinically evident disease. Consequently, there is great interest in determining which T cells subsets mediate anti-mycobacterial immunity, delineating their effector functions. On the other hand, many aspects remain unsolved in understanding why some individuals are protected from Mtb infection while others go on to develop disease. Several studies have demonstrated that CD4
+ T cells are involved in protection against Mtb, as supported by the evidence that CD4+ T cell depletion is responsible for Mtb reactivation in HIV-infected individuals. There are many subsets of CD4+ T cells, such as T-helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and all these subsets cooperate or interfere with each other to control infection; the dominant subset may differ between active and latent Mtb infection cases. Mtb-specific-CD4+ Th1 cell response is considered to have a protective role for the ability to produce cytokines such as IFN-γ or TNF-α that contribute to the recruitment and activation of innate immune cells, like monocytes and granulocytes. Thus, while other antigen (Ag)-specific T cells such as CD8+ T cells, natural killer (NK) cells, γδ T cells, and CD1-restricted T cells can also produce IFN-γ during Mtb infection, they cannot compensate for the lack of CD4+ T cells. The detection of Ag-specific cytokine production by intracellular cytokine staining (ICS) and the use of flow cytometry techniques are a common routine that supports the studies aimed at focusing the role of the immune system in infectious diseases. Flow cytometry permits to evaluate simultaneously the presence of different cytokines that can delineate different subsets of cells as having "multifunctional/polyfunctional" profile. It has been proposed that polyfunctional T cells, are associated with protective immunity toward Mtb, in particular it has been highlighted that the number of Mtb-specific T cells producing a combination of IFN-γ, IL-2, and/or TNF-α may be correlated with themycobacterial load, while other studies have associated the presence of this particular functional profile as marker of TB disease activity. Although the role of CD8T cells in TB is less clear than CD4 T cells, they are generally considered to contribute to optimal immunity and protection. CD8T cells possess a number of anti-microbial effector mechanisms that are less prominent or absent in CD4 Th1 and Th17 T cells. The interest in studying CD8T cells that are either MHC-class Ia or MHC-class Ib-restricted, has gained more attention. These studies include the role of HLA-E-restricted cells, lung mucosal-associated invariant T-cells (MAIT), and CD1-restricted cells. Nevertheless, the knowledge about the role of CD8+ T cells in Mtb infection is relatively new and recent studies have delineated that CD8 T cells, which display a functional profile termed "multifunctional," can be a better marker of protection inTB than CD4+ T cells. Their effector mechanisms could contribute to control Mtb infection, as upon activation, CD8 T cells release cytokines or cytotoxic molecules, which cause apoptosis of target cells. Taken together, the balance of the immune response in the control of infection and possibly bacterial eradication is important in understanding whether the host immune response will be appropriate in contrasting the infection or not, and, consequently, the inability of the immune response, will determine the dissemination and the transmission of bacilli to new subjects. In conclusion, the recent highlights on the role of different functional signatures of T cell subsets in the immune response toward Mtb infection will be discerned in this review, in order to summarize what is known about the immune response in human TB. In particular, we will discuss the role of CD4 and CD8T cells in contrasting the advance of the intracellular pathogen in already infected people or the progression to active disease in subjects with latent infection. All the information will be aimed at increasing the knowledge of this complex disease in order to improve diagnosis, prognosis, drug treatment, and vaccination. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
27. Immunity and Nutrition: The Right Balance in Inflammatory Bowel Disease.
- Author
-
Tamburini, Bartolo, La Manna, Marco Pio, La Barbera, Lidia, Mohammadnezhad, Leila, Badami, Giusto Davide, Shekarkar Azgomi, Mojtaba, Dieli, Francesco, and Caccamo, Nadia
- Subjects
- *
INFLAMMATORY bowel diseases , *COLORECTAL cancer , *IMMUNITY , *DYSBIOSIS , *INTESTINAL diseases ,DEVELOPING countries - Abstract
Inflammatory bowel disease (IBD) is an increasingly urgent medical problem that strongly impairs quality of life for patients. A global rise in incidence has been observed over the last few decades, with the highest incidence rates recorded in North America and Europe. Still, an increased incidence has been reported in the last ten years in newly industrialized countries in Asia, including China and India, both with more than one billion inhabitants. These data underline that IBD is an urgent global health problem. In addition, it is estimated that between 20% and 30% of IBD patients will develop colorectal cancer (CRC) within their lifetime and CRC mortality is approximately 50% amongst IBD patients. Although the exact etiology of IBD is still being defined, it is thought to be due to a complex interaction between many factors, including defects in the innate and adaptive immune system; microbial dysbiosis, i.e., abnormal levels of, or abnormal response to, the gastrointestinal microbiome; a genetic predisposition; and several environmental factors. At present, however, it is not fully understood which of these factors are the initiators of inflammation and which are compounders. The purpose of this review is to analyze the complex balance that exists between these elements to maintain intestinal homeostasis and prevent IBD or limit adverse effects on people's health. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
28. Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways.
- Author
-
Pucci, Marzia, Raimondo, Stefania, Urzì, Ornella, Moschetti, Marta, Di Bella, Maria Antonietta, Conigliaro, Alice, Caccamo, Nadia, La Manna, Marco Pio, Fontana, Simona, and Alessandro, Riccardo
- Subjects
EXTRACELLULAR vesicles ,CELLULAR signal transduction ,PROGRAMMED cell death 1 receptors ,TOLL-like receptors ,PROGRAMMED death-ligand 1 ,CYTOKINES - Abstract
Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), and other inflammatory cytokines as well as of the underlying molecular mechanisms were evaluated. Our results indicate that SEVs can significantly upregulate the expressions of PD-L1 and IL-6 at both the mRNA and protein levels and can activate the STAT3 signaling pathway. Furthermore, we identified the TLR4/NF-kB pathway as a convergent mechanism for SEV-mediated PD-L1 expression. Overall, these preliminary data suggest that SEVs contribute to the formation of an immunosuppressive microenvironment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
29. A Rapid and Simple Multiparameter Assay to Quantify Spike-Specific CD4 and CD8 T Cells after SARS-CoV-2 Vaccination: A Preliminary Report.
- Author
-
Azgomi, Mojtaba Shekarkar, La Manna, Marco Pio, Badami, Giusto Davide, Ragonese, Paolo, Trizzino, Antonino, Dieli, Francesco, and Caccamo, Nadia
- Subjects
T cells ,SARS-CoV-2 ,CD8 antigen ,CD4 antigen ,IMMUNOLOGIC memory - Abstract
mRNA and Adenovirus vaccines for COVID-19 are used to induce humoral and cell-mediated immunity, with the aim to generate both SARS-CoV-2 B and T memory cells. In present study, we described a simple assay to detect and quantify Spike-specific CD4
+ and CD8+ T cell responses induced by vaccination in healthy donors and in subjects with B cell compart impairment, in which antibody response is absent due to primary immunodeficiencies or CD20 depleting therapy. We detect and quantified memory T cell immune responses against SARS-CoV-2 evocated by vaccination in both groups, irrespective to the humoral response. Furthermore, we identified TNF-α as the main cytokine produced by T memory cells, after antigen-specific stimulation in vitro, that could be considered, other than IFN-γ, an additional biomarker of induction of T memory cells upon vaccination. Further studies on the vaccine-induced T cell responses could be crucial, not only in healthy people but also in immunocompromised subjects, where antigen specific T cells responses play a protective role against SARS-CoV-2. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
30. Immunoregulatory role of Jα281 T cells in aged mice developing lupus-like nephritis.
- Author
-
Sireci, Guido, Russo, Domenica, Dieli, Francesco, Porcelli, Steven A., Taniguchi, Masaru, La Manna, Marco Pio, Di Liberto, Diana, Scarpa, Francesco, and Salerno, Alfredo
- Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Vα14Jα281 chains paired with some Vβ domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jα281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jα281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jα281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgGsubclass. In spleens of aged Jα281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jα281cells, probably associated with the activation of marginal zone B cells. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
31. Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines.
- Author
-
Torina, Alessandra, Blanda, Valeria, Villari, Sara, Piazza, Antonio, La Russa, Francesco, Grippi, Francesca, La Manna, Marco Pio, Di Liberto, Diana, de la Fuente, José, and Sireci, Guido
- Subjects
IMMUNE response ,T helper cells ,CELLULAR immunity ,VACCINE development ,VACCINES ,CYTOTOXIC T cells - Abstract
Tick-transmitted pathogens cause infectious diseases in both humans and animals. Different types of adaptive immune mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen antigens or indirectly through soluble factors, such as cytokines and/or chemokines, secreted by host cells as response. Adaptive immunity effectors, such as antibody secretion and cytotoxic and/or T helper cell responses, are mainly involved in the late and long-lasting protective immune response. Proteins and/or epitopes derived from pathogens and tick vectors have been isolated and characterized for the immune response induced in different hosts. This review was focused on the interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T- and/or B cell-mediated adaptive immunity, describing the efforts to define immunodominant proteins or epitopes for vaccine development and/or immunotherapeutic purposes. A better understanding of these mechanisms of host immunity could lead to the assessment of possible new immunotherapies for these pathogens as well as to the prediction of possible new candidate vaccine antigens. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
32. Innate Immune Response to Tick-Borne Pathogens: Cellular and Molecular Mechanisms Induced in the Hosts.
- Author
-
Torina, Alessandra, Villari, Sara, Blanda, Valeria, Vullo, Stefano, La Manna, Marco Pio, Shekarkar Azgomi, Mojtaba, Di Liberto, Diana, de la Fuente, José, and Sireci, Guido
- Subjects
IMMUNE response ,KILLER cells ,RICKETTSIAL diseases ,RICKETTSIA ,TUMOR necrosis factors ,CASTOR bean tick ,NATURAL immunity ,SCAFFOLD proteins - Abstract
Many pathogens are transmitted by tick bites, including Anaplasma spp., Ehrlichia spp., Rickettsia spp., Babesia and Theileria sensu stricto species. These pathogens cause infectious diseases both in animals and humans. Different types of immune effector mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen-derived antigens or indirectly by molecules released by host cells binding to these antigens. The components of innate immunity, such as natural killer cells, complement proteins, macrophages, dendritic cells and tumor necrosis factor alpha, cause a rapid and intense protection for the acute phase of infectious diseases. Moreover, the onset of a pro-inflammatory state occurs upon the activation of the inflammasome, a protein scaffold with a key-role in host defense mechanism, regulating the action of caspase-1 and the maturation of interleukin-1β and IL-18 into bioactive molecules. During the infection caused by different microbial agents, very similar profiles of the human innate immune response are observed including secretion of IL-1α, IL-8, and IFN-α, and suppression of superoxide dismutase, IL-1Ra and IL-17A release. Innate immunity is activated immediately after the infection and inflammasome-mediated changes in the pro-inflammatory cytokines at systemic and intracellular levels can be detected as early as on days 2–5 after tick bite. The ongoing research field of "inflammasome biology" focuses on the interactions among molecules and cells of innate immune response that could be responsible for triggering a protective adaptive immunity. The knowledge of the innate immunity mechanisms, as well as the new targets of investigation arising by bioinformatics analysis, could lead to the development of new methods of emergency diagnosis and prevention of tick-borne infections. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
33. B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma
- Author
-
Leila Mohammadnezhad, Mojtaba Shekarkar Azgomi, Marco Pio La Manna, Giuliana Guggino, Cirino Botta, Francesco Dieli, Nadia Caccamo, Mohammadnezhad, Leila, Shekarkar Azgomi, Mojtaba, La Manna, Marco Pio, Guggino, Giuliana, Botta, Cirino, Dieli, Francesco, and Caccamo, Nadia
- Subjects
non-hodgkins lymphoma ,primary Sjogren syndrome ,DLBCL ,cell signaling ,BCR ,Organic Chemistry ,General Medicine ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
Primary Sjogren syndrome (pSS) is the second most common autoimmune disorder worldwide, which, in the worst scenario, progresses to Non-Hodgkin Lymphoma (NHL). Despite extensive studies, there is still a lack of knowledge about developing pSS for NHL. This study focused on cells’ signaling in pSS progression to the NHL type of diffuse large B-cell lymphoma (DLBCL). Using bulk RNA and single cell analysis, we found five novel pathologic-independent clusters in DLBCL based on cells’ signaling. B-cell receptor (BCR) signaling was identified as the only enriched signal in DLBCL and pSS peripheral naive B-cells or salivary gland-infiltrated cells. The evaluation of the genes in association with BCR has revealed that targeting CD79A, CD79B, and LAMTOR4 as the shared genes can provide novel biomarkers for pSS progression into lymphoma.
- Published
- 2023
- Full Text
- View/download PDF
34. Impact of antiretroviral and tuberculosis therapies on CD4+ and CD8+ HIV/M. tuberculosis-specific T-cell in co-infected subjects.
- Author
-
Chiacchio, Teresa, Petruccioli, Elisa, Vanini, Valentina, Cuzzi, Gilda, La Manna, Marco Pio, Orlando, Valentina, Pinnetti, Carmela, Sampaolesi, Alessandro, Antinori, Andrea, Caccamo, Nadia, and Goletti, Delia
- Subjects
- *
ANTIRETROVIRAL agents , *TUBERCULOSIS treatment , *CD4 antigen , *CD8 antigen , *T cells - Abstract
Background Human Immunodeficiency Virus (HIV) infection is a risk factor for tuberculosis (TB). Antiretroviral therapy (ART) changed HIV clinical management but it is still unclear how pre-existing HIV/Mycobacterium tuberculosis (Mtb)-specific CD4 + and CD8 + T-cells are restored. Aim to evaluate the impact of ART and TB therapies on the functional and phenotypic profile of Mtb-specific antigen-response of CD4 + and CD8 + T-cells in prospectively enrolled HIV-TB co-infected patients. Methods ART-naïve HIV-infected patients, with or without active TB or latent TB infection (LTBI), were enrolled before and after starting ART and TB therapies. Peripheral blood mononuclear cells (PBMC) were stimulated overnight with Mtb and HIV antigens (GAG). Cytokine expression and phenotype profile were evaluated by flow cytometry. Cytomegalovirus (CMV) and staphylococcal enterotoxin B (SEB) were also used. Results The median of absolute number of CD4 + T-cells increased after ART and TB therapies in all groups analyzed, while the median of absolute number of CD8 + T-cells decreases in HIV and HIV-LTBI groups. Treatments significantly increased the frequency of Mtb-specific CD4 + T-cells in the HIV-LTBI (p = 0.015) with a rise of the central memory compartment. The magnitude of the CD4 + T-cell response to HIV-GAG significantly increased in active TB (p = 0.03), whereas the magnitude of CMV-specific CD4 + T-cell response decreased in all the groups. Similarly, the treatments increased the number of Mtb-specific CD8 + responders in both HIV-LTBI and HIV-TB groups, whereas the phenotype distribution was dependent on the antigens used and on the stage of infection/disease. Conclusions After therapies the median of absolute number and the proportion of CD4 + T-cells increased in all groups whereas the median of absolute count and proportion of CD8 + T-cells decreased in the HIV and HIV-LTBI subjects. Interestingly, an increased frequency of CD4 + T-cell response to RD1 proteins in HIV-LTBI subjects was found. These results contribute to a better understanding of the effect of ART and TB therapies on the modulation of Mtb-specific CD4 + and CD8 + T-cells subsets. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
35. The janus face of NKT cell function in autoimmunity and infectious diseases
- Author
-
Giuliana Guggino, Alessandra Torina, Marco Pio La Manna, Guido Sireci, Torina, Alessandra, Guggino, Giuliana, La Manna, Marco Pio, and Sireci, Guido
- Subjects
0301 basic medicine ,glycolipids ,Autoimmunity ,Review ,Adaptive Immunity ,medicine.disease_cause ,Catalysi ,immunology ,lcsh:Chemistry ,0302 clinical medicine ,T-Lymphocyte Subsets ,lcsh:QH301-705.5 ,Spectroscopy ,Innate lymphoid cell ,hemic and immune systems ,Computer Science Applications1707 Computer Vision and Pattern Recognition ,General Medicine ,NKT ,Natural killer T cell ,Acquired immune system ,Computer Science Applications ,Cell biology ,CD1D ,microbes ,Cell type ,chemical and pharmacologic phenomena ,Glycolipid ,Biology ,CD1d ,Communicable Diseases ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Animals ,Humans ,Microbe ,Physical and Theoretical Chemistry ,Molecular Biology ,Inflammation ,T-cell receptor ,Organic Chemistry ,Models, Immunological ,Alpha-galactosylceramide ,Glycolipids ,Microbes ,Sulfatide ,Immunity, Innate ,Settore MED/16 - Reumatologia ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,biology.protein ,Natural Killer T-Cells ,CD8 ,030215 immunology - Abstract
Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defence against infections but, on the other hand, their effector functions can be involved in the pathogenesis of several inflammatory disorders due to their exposure to different microbial or self antigens, respectively. A deep understanding of the biology and functions of type I, II and NKT-like cells as well as their interplay with cell types acting in innate (Neuthrophils, Innate Lymphoid cells, Machrophages and Dendritic cells) and adaptive immunity (CD4+,CD8+ and Double Negative T cells) should be important to design potential immunotherapies for infectious and autoimmune diseases.
- Published
- 2018
36. Downregulation of miRNA17-92 cluster marks Vγ9Vδ2 T cells from patients with rheumatoid arthritis
- Author
-
Laura Saieva, Marco Pio La Manna, Roberto Giacomelli, Francesco Ciccia, Valentina Orlando, Giuliana Guggino, Francesco Dieli, Giovanni Triolo, Riccardo Alessandro, Piero Ruscitti, Paola Cipriani, Nadia Caccamo, Guggino, Giuliana, Orlando, Valentina, Saieva, Laura, Ruscitti, Piero, Cipriani, Paola, La Manna, Marco Pio, Giacomelli, Roberto, Alessandro, Riccardo, Triolo, Giovanni, Ciccia, Francesco, Dieli, Francesco, Caccamo, Nadia, Guggino, G., Orlando, V., Saieva, L., Ruscitti, P., Cipriani, P., La Manna, M. P., Giacomelli, R., Alessandro, R., Triolo, G., Ciccia, F., Dieli, F., and Caccamo, N.
- Subjects
Adult ,Male ,0301 basic medicine ,miRNA17–92 ,lcsh:Diseases of the musculoskeletal system ,Inflammatory cytokine ,Immunology ,Down-Regulation ,Biology ,γδ T cells ,Proinflammatory cytokine ,Flow cytometry ,Arthritis, Rheumatoid ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Rheumatology ,T-Lymphocyte Subsets ,Inflammatory cytokines ,miRNA17-92 ,Rheumatoid arthritis ,Immunology and Allergy ,microRNA ,medicine ,Humans ,Rheumatoid arthriti ,γδ T cell ,medicine.diagnostic_test ,Effector ,Interleukin ,Middle Aged ,Phenotype ,MicroRNAs ,Settore MED/16 - Reumatologia ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,lcsh:RC925-935 ,Research Article - Abstract
Background We aimed to evaluate the phenotype, function, and microRNA (miRNA)17–92 cluster expression in Vγ9Vδ2 T-cell subsets and the correlation with immune response in rheumatoid arthritis (RA) patients. Methods Peripheral blood from 10 early RA untreated patients and 10 healthy donors (HD) was obtained. Polyclonal Vγ9Vδ2 T-cell lines were generated and analysed by flow cytometry. Analysis of miRNA17–92 cluster expression was performed by real-time polymerase chain reaction (RT-PCR), and expression of mRNA target genes was also studied. Results A remarkable change in the distribution of Vγ9Vδ2 T-cell functional subsets was observed in the peripheral blood of RA patients compared with HD, with an expansion of effector subsets and reduction of naive cells which was accompanied by modifications in proinflammatory cytokine expression. Vγ9Vδ2 T cells with a TEM (effector memory) phenotype and producing proinflammatory cytokines were correlated with disease activity score (DAS28). The comparison of miRNA expression among Vγ9Vδ2 T-cell subsets from RA patients and HD showed a lower level of miR-106a-5p and miR-20a-5p, and a higher level of miR-21a-5p, among Vγ9Vδ2 TEM cells, and a lower level of miR-19b-3p among Vγ9Vδ2 TCM (central memory) cells was also found. These differentially expressed miRNAs correlated with higher levels of expression of interleukin (IL)-8, IL-6, and PDCD4 genes. Conclusions Our results provide evidence for a role of miR-106a, miR-19-3p, miR-20a, and miR-21a in the regulation of Vγ9Vδ2 T-cell function in RA patients and suggest the possibility that the miRNA17–92 family and Vγ9Vδ2 T cells contribute to the pathogenesis of RA.
- Published
- 2018
37. Deep Immunoprofiling of Large-Scale Tuberculosis Dataset at Single Cell Resolution Reveals a CD81 bright γδ T Cell Population Associated with Latency.
- Author
-
Shekarkar Azgomi M, Badami GD, Di Caro M, Tamburini B, Fallo M, Dieli C, Ebrahimi K, Dieli F, La Manna MP, and Caccamo N
- Subjects
- Humans, Tetraspanin 28 metabolism, Single-Cell Analysis, Latent Tuberculosis immunology, Tuberculosis immunology, Tuberculosis microbiology, Female, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Adult, Male, Receptors, Antigen, T-Cell, gamma-delta metabolism, Mycobacterium tuberculosis immunology
- Abstract
Tuberculosis (TB) remains one of the leading causes of death among infectious diseases, with 10.6 million new cases and 1.3 million deaths reported in 2022, according to the most recent WHO report. Early studies have shown an expansion of γδ T cells following TB infection in both experimental models and humans, indicating their abundance among lung lymphocytes and suggesting a role in protective immune responses against Mycobacterium tuberculosis ( M. tuberculosis ) infection. In this study, we hypothesized that distinct subsets of γδ T cells are associated with either protection against or disease progression in TB. To explore this, we applied large-scale scRNA-seq and bulk RNA-seq data integration to define the phenotypic and molecular characteristics of peripheral blood γδ T cells. Our analysis identified five unique γδ T subclusters, each with distinct functional profiles. Notably, we identified a unique cluster significantly enriched in the TCR signaling pathway, with high CD81 expression as a conserved marker. This distinct molecular signature suggests a specialized role for this cluster in immune signaling and regulation of immune response against M. tuberculosis . Flow cytometry confirmed our in silico results, showing that the mean fluorescence intensity (MFI) values of CD81 expression on γδ T cells were significantly increased in individuals with latent TB infection (TBI) compared to those with active TB (ATB). This finding underscores the importance of CD81 and its associated signaling mechanisms in modulating the activity and function of γδ T cells under TBI conditions, providing insights into potential therapeutic targets for TB management.
- Published
- 2024
- Full Text
- View/download PDF
38. The potential relationship between PU.1 and IL-9 in the development of arthritis.
- Author
-
La Barbera L, Rizzo C, Lo Pizzo M, La Manna MP, Ciccia F, and Guggino G
- Subjects
- Humans, Interleukin-9, Arthritis etiology
- Published
- 2023
- Full Text
- View/download PDF
39. Interleukin 9 neutralisation reduces collagen-induced arthritis severity in mouse models.
- Author
-
Guggino G, La Manna MP, Di Liberto D, Lo Pizzo M, Grasso G, Schinocca C, Rizzo A, Lentini VL, Lo Presti E, Shekarkar Azgomi M, Dieli F, Sireci G, and Ciccia F
- Subjects
- Animals, Mice, Interleukin-9 therapeutic use, Mice, Inbred DBA, Disease Models, Animal, Tumor Necrosis Factor-alpha therapeutic use, Arthritis, Experimental pathology
- Abstract
Objectives: Interleukin 9 (IL-9) is a mediator of tissue damage in several inflammatory diseases. In this study we aimed to evaluate the effects of in vivo IL-9 neutralisation in mice developing collagen induced arthritis (CIA)., Methods: DBA/1 were immunised with collagen in Freund's complete adjuvant (CFA) to induce arthritis. Anti-IL-9 mAb was injected in mice after the onset of arthritis (Group A) or on the same day as sensitisation and again on the day of the challenge (Group B). Histological analysis was performed in joints of mice and spleen cells were also analysed by flow cytometry. A geneset analysis was carried out on whole tarsal joint tissue transcriptomes., Results: IL-9 was over-expressed in swollen joints of mice developing arthritis. Treatment with anti-IL-9 mAb after arthritis onset efficiently down-modulated the severity of joint inflammation. Similarly, anti-IL-9 mAb administered on the same day as sensitisation and on the day of challenge also delayed the onset of arthritis. Anti-IL-9 mAb injection after the onset of arthritis was associated with a decrease of CD4+ TNF-α+ cells and an increase of CD4+ FoxP3+ IL-10+ cells. Geneset analysis in CIA showed an up-regulation of GATA3 with no significant direct interactions between IL-9 and GATA3, which instead was mediated by IL-5 through STAT6., Conclusions: Our results suggest that IL-9 is involved in the immunopathogenesis of CIA. Further implications for the clinical translation of our findings are discussed.
- Published
- 2023
- Full Text
- View/download PDF
40. Interleukin-6 Is a Promising Marker of COVID-19 in Children: A Case Series of 2 Brothers with Severe COVID-19 Pneumonia.
- Author
-
Maggio MC, Failla MC, Giordano S, La Manna MP, and Sireci G
- Subjects
- Aged, Cough, Fever, Humans, Infant, Interleukin-6, Male, Methylprednisolone therapeutic use, Pandemics, SARS-CoV-2, Siblings, COVID-19, Pneumonia
- Abstract
BACKGROUND To date, Coronavirus disease 2019 (COVID-19) remains a global health concern, with fatalities mostly in older age groups with underlying medical conditions, while children are less likely to manifest severe symptoms. CASE REPORT We describe the clinical cases of 2 brothers admitted to our Children's Hospital for persistent fever and cough during the COVID-19 pandemic. Case 1. A 1.5-year-old boy had fever, expiratory dyspnea, desaturation, oxygen saturation 94-96% with O2, and bilateral hissing and crackling rales. His interleukin-6 level in the acute phase of the disease was 100.41 and at the resolution it was 46.2 pg/ml. Treatment with amoxicillin plus clavulanic acid, methylprednisolone, and O2 allowed progressive improvement of clinical conditions and laboratory data. Case 2. A 3-month-old toddler was admitted to our hospital for fever, cough, and tachypnea, which started 2 days before hospitalization. He had fever, cough, conjunctivitis, mucous rhinorrhea, and 99% oxygen saturation on room air. Thorax auscultation showed whistles and buzzes. He had a positive molecular test result from a COVID-19 swab. Interleukin-6 levels during all the phases of the disease were <6.25 pg/ml. The chest X-ray was normal. Treatment with azithromycin and methylprednisolone was followed by progressive improvement of clinical conditions. CONCLUSIONS These cases support the strong correlation between interleukin-6 levels and severe clinical manifestations such as COVID-19 pneumonia, and this marker predicts a more severe clinical outcome in children. Testing serum levels of interleukin-6 in children with COVID-19 could be useful to better understand the outcome of lung damage.
- Published
- 2022
- Full Text
- View/download PDF
41. Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8 + T Cells.
- Author
-
La Manna MP, Shekarkar Azgomi M, Tamburini B, Badami GD, Mohammadnezhad L, Dieli F, and Caccamo N
- Subjects
- Memory T Cells, Phenotype, Stem Cells, CD8-Positive T-Lymphocytes, Immunologic Memory
- Abstract
The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases. Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as "memory". T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we examine recent developments in the characterization of the heterogeneity of the memory T cell compartment. In particular, we focus on the emerging role of CD8
+ TRM and TSCM cells, providing evidence on how their immunometabolism or modulation can play a vital role in their generation and maintenance in chronic conditions such as infections or autoimmune diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 La Manna, Shekarkar Azgomi, Tamburini, Badami, Mohammadnezhad, Dieli and Caccamo.)- Published
- 2022
- Full Text
- View/download PDF
42. A Rapid and Simple Multiparameter Assay to Quantify Spike-Specific CD4 and CD8 T Cells after SARS-CoV-2 Vaccination: A Preliminary Report.
- Author
-
Shekarkar Azgomi M, La Manna MP, Badami GD, Ragonese P, Trizzino A, Dieli F, and Caccamo N
- Abstract
mRNA and Adenovirus vaccines for COVID-19 are used to induce humoral and cell-mediated immunity, with the aim to generate both SARS-CoV-2 B and T memory cells. In present study, we described a simple assay to detect and quantify Spike-specific CD4
+ and CD8+ T cell responses induced by vaccination in healthy donors and in subjects with B cell compart impairment, in which antibody response is absent due to primary immunodeficiencies or CD20 depleting therapy. We detect and quantified memory T cell immune responses against SARS-CoV-2 evocated by vaccination in both groups, irrespective to the humoral response. Furthermore, we identified TNF-α as the main cytokine produced by T memory cells, after antigen-specific stimulation in vitro, that could be considered, other than IFN-γ, an additional biomarker of induction of T memory cells upon vaccination. Further studies on the vaccine-induced T cell responses could be crucial, not only in healthy people but also in immunocompromised subjects, where antigen specific T cells responses play a protective role against SARS-CoV-2.- Published
- 2021
- Full Text
- View/download PDF
43. HLA-E-restricted CD8 + T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Coinfection.
- Author
-
La Manna MP, Orlando V, Prezzemolo T, Di Carlo P, Cascio A, Delogu G, Poli G, Sullivan LC, Brooks AG, Dieli F, and Caccamo N
- Subjects
- Adult, Antigens, Bacterial immunology, Down-Regulation immunology, Female, Humans, Lymphocyte Activation immunology, Lymphocyte Count methods, Male, Middle Aged, HLA-E Antigens, CD8-Positive T-Lymphocytes immunology, Coinfection immunology, HIV Infections immunology, HIV-1 immunology, HLA-A2 Antigen immunology, Histocompatibility Antigens Class I immunology, Mycobacterium tuberculosis immunology, Tuberculosis immunology
- Abstract
We investigated the contribution of human leukocyte antigen A2 (HLA-A2) and HLA-E-restricted CD8
+ T cells in patients with Mycobacterium tuberculosis and human immunodeficiency virus 1 (HIV-1) coinfection. HIV-1 downregulates HLA-A, -B, and -C molecules in infected cells, thus influencing recognition by HLA class I-restricted CD8+ T cells but not by HLA-E-restricted CD8+ T cells, owing to the inability of the virus to downmodulate their expression. Therefore, antigen-specific HLA-E-restricted CD8+ T cells could play a protective role in Mycobacterium tuberculosis and HIV-1 coinfection. HLA-E- and HLA-A2-restricted Mycobacterium tuberculosis -specific CD8+ T cells were tested in vitro for cytotoxic and microbicidal activities, and their frequencies and phenotypes were evaluated ex vivo in patients with active tuberculosis and concomitant HIV-1 infection. HIV-1 and Mycobacterium tuberculosis coinfection caused downmodulation of HLA-A2 expression in human monocyte-derived macrophages associated with resistance to lysis by HLA-A2-restricted CD8+ T cells and failure to restrict the growth of intracellular Mycobacterium tuberculosis . Conversely, HLA-E surface expression and HLA-E-restricted cytolytic and microbicidal CD8 responses were not affected. HLA-E-restricted and Mycobacterium tuberculosis -specific CD8+ T cells were expanded in the circulation of patients with Mycobacterium tuberculosis /HIV-1 coinfection, as measured by tetramer staining, but displayed a terminally differentiated and exhausted phenotype that was rescued in vitro by anti-PD-1 (programmed cell death protein 1) monoclonal antibody. Together, these results indicate that HLA-E-restricted and Mycobacterium tuberculosis -specific CD8+ T cells in patients with Mycobacterium tuberculosis /HIV-1 coinfection have an exhausted phenotype and fail to expand in vitro in response to antigen stimulation, which can be restored by blocking the PD-1 pathway using the specific monoclonal antibody nivolumab.- Published
- 2020
- Full Text
- View/download PDF
44. Analysis of interferon-gamma producing cells during infections by Yersinia enterocolitica O:9 and Brucella abortus in cattle.
- Author
-
Agnone A, La Manna MP, Vesco G, Gargano V, Macaluso G, Dieli F, Sireci G, and Villari S
- Subjects
- Animals, Cattle, Flow Cytometry veterinary, Leukocytes, Mononuclear immunology, Brucella abortus physiology, Brucellosis, Bovine immunology, Interferon-gamma immunology, Yersinia Infections immunology, Yersinia enterocolitica physiology
- Abstract
One of the major constraints in the diagnosis of animal brucellosis is the cross-reactivity that occurs between Brucella and Yersinia surface antigens. With the aim to find a method to distinguish Brucella from Yersinia infection, the expansion of interferon gamma producing (IFN-γ+) T cell subsets obtained from peripheral blood mononuclear cells (PBMC) isolated from cattle either infected by Brucella abortus or experimentally immunized with Yersinia enterocolitica O:9 were compared. The lymphocytes were analyzed by flow cytometry after PBMC were in vitro re-exposed to Yersinia or Brucella antigens. The results highlighted a statistically significant difference in the expansion of the CD4+ and CD8+ IFN-γ+ T cells occurring when PBMC of animals immunized with Yersinia are in vitro exposed to Y. enterocolitica O:9 antigen but not to Brucella antigen. This method could thus be suggested in those cases where results obtained by serodiagnosis need to be further clarified.
- Published
- 2019
- Full Text
- View/download PDF
45. Functional Signatures of Human CD4 and CD8 T Cell Responses to Mycobacterium tuberculosis.
- Author
-
Prezzemolo T, Guggino G, La Manna MP, Di Liberto D, Dieli F, and Caccamo N
- Abstract
With 1.4 million deaths and 8.7 million new cases in 2011, tuberculosis (TB) remains a global health care problem and together with HIV and Malaria represents one of the three infectious diseases world-wide. Control of the global TB epidemic has been impaired by the lack of an effective vaccine, by the emergence of drug-resistant forms of Mycobacterium tuberculosis (Mtb) and by the lack of sensitive and rapid diagnostics. It is estimated, by epidemiological reports, that one third of the world's population is latently infected with Mtb, but the majority of infected individuals develop long-lived protective immunity, which controls and contains Mtb in a T cell-dependent manner. Development of TB disease results from interactions among the environment, the host, and the pathogen, and known risk factors include HIV co-infection, immunodeficiency, diabetes mellitus, overcrowding, malnutrition, and general poverty; therefore, an effective T cell response determines whether the infection resolves or develops into clinically evident disease. Consequently, there is great interest in determining which T cells subsets mediate anti-mycobacterial immunity, delineating their effector functions. On the other hand, many aspects remain unsolved in understanding why some individuals are protected from Mtb infection while others go on to develop disease. Several studies have demonstrated that CD4(+) T cells are involved in protection against Mtb, as supported by the evidence that CD4(+) T cell depletion is responsible for Mtb reactivation in HIV-infected individuals. There are many subsets of CD4(+) T cells, such as T-helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and all these subsets co-operate or interfere with each other to control infection; the dominant subset may differ between active and latent Mtb infection cases. Mtb-specific-CD4(+) Th1 cell response is considered to have a protective role for the ability to produce cytokines such as IFN-γ or TNF-α that contribute to the recruitment and activation of innate immune cells, like monocytes and granulocytes. Thus, while other antigen (Ag)-specific T cells such as CD8(+) T cells, natural killer (NK) cells, γδ T cells, and CD1-restricted T cells can also produce IFN-γ during Mtb infection, they cannot compensate for the lack of CD4(+) T cells. The detection of Ag-specific cytokine production by intracellular cytokine staining (ICS) and the use of flow cytometry techniques are a common routine that supports the studies aimed at focusing the role of the immune system in infectious diseases. Flow cytometry permits to evaluate simultaneously the presence of different cytokines that can delineate different subsets of cells as having "multifunctional/polyfunctional" profile. It has been proposed that polyfunctional T cells, are associated with protective immunity toward Mtb, in particular it has been highlighted that the number of Mtb-specific T cells producing a combination of IFN-γ, IL-2, and/or TNF-α may be correlated with the mycobacterial load, while other studies have associated the presence of this particular functional profile as marker of TB disease activity. Although the role of CD8 T cells in TB is less clear than CD4 T cells, they are generally considered to contribute to optimal immunity and protection. CD8 T cells possess a number of anti-microbial effector mechanisms that are less prominent or absent in CD4 Th1 and Th17 T cells. The interest in studying CD8 T cells that are either MHC-class Ia or MHC-class Ib-restricted, has gained more attention. These studies include the role of HLA-E-restricted cells, lung mucosal-associated invariant T-cells (MAIT), and CD1-restricted cells. Nevertheless, the knowledge about the role of CD8(+) T cells in Mtb infection is relatively new and recent studies have delineated that CD8 T cells, which display a functional profile termed "multifunctional," can be a better marker of protection in TB than CD4(+) T cells. Their effector mechanisms could contribute to control Mtb infection, as upon activation, CD8 T cells release cytokines or cytotoxic molecules, which cause apoptosis of target cells. Taken together, the balance of the immune response in the control of infection and possibly bacterial eradication is important in understanding whether the host immune response will be appropriate in contrasting the infection or not, and, consequently, the inability of the immune response, will determine the dissemination and the transmission of bacilli to new subjects. In conclusion, the recent highlights on the role of different functional signatures of T cell subsets in the immune response toward Mtb infection will be discerned in this review, in order to summarize what is known about the immune response in human TB. In particular, we will discuss the role of CD4 and CD8 T cells in contrasting the advance of the intracellular pathogen in already infected people or the progression to active disease in subjects with latent infection. All the information will be aimed at increasing the knowledge of this complex disease in order to improve diagnosis, prognosis, drug treatment, and vaccination.
- Published
- 2014
- Full Text
- View/download PDF
46. Prophylaxis of lipopolysaccharide-induced shock by alpha-galactosylceramide.
- Author
-
Sireci G, La Manna MP, Di Liberto D, Lo Dico M, Taniguchi M, Dieli F, and Salerno A
- Subjects
- Adjuvants, Immunologic therapeutic use, Animals, Cytokines analysis, Disease Models, Animal, Mice, Mice, Inbred C57BL, Time Factors, Galactosylceramides therapeutic use, Lipopolysaccharides toxicity, Shock, Septic chemically induced, Shock, Septic prevention & control
- Abstract
The NKT cell ligand alpha-galactosylceramide and its synthetic homologue KRN7000 stimulate rapid and copious secretion of IFN-gamma and TNF-alpha release, both of which are key mediators of LPS-induced shock. We showed that KRN7000, injected before or within 2 h after LPS challenge, was able to prevent endotoxic shock. KRN7000 induced survival when the mice were injected 6, 9, or 12 days before the first injection of LPS, and this protective effect was associated with reduction upon subsequent challenge in the levels of IFN-gamma, TNF-alpha, MCP-1, and an increase of IL-10. Further analysis showed that the animals treated with KRN7000 prior to LPS challenge had lower numbers of F4/80+, NKT, and NK cells and lower percentages of NKT cells that stained for intracytoplasmic IFN-gamma when compared with mice that were not treated with KRN7000. When MCP-1 was injected in KRN7000-treated mice, the lethal effect of LPS challenge was restored, and the numbers of F4/80+, NKT, and NK cells increased to levels similar to those in untreated mice following LPS challenge. Taken together, our data demonstrated that KRN7000, injected from 6 to 12 days before the first administration of LPS, prevented endotoxin shock by inhibiting IFN-gamma, TNF-alpha, and MCP-1 release.
- Published
- 2008
- Full Text
- View/download PDF
47. Anti-16-kilodalton mycobacterial protein immunoglobulin m levels in healthy but purified protein derivative-reactive children decrease after chemoprophylaxis.
- Author
-
Sireci G, Dieli F, Di Liberto D, Buccheri S, La Manna MP, Scarpa F, Macaluso P, Romano A, Titone L, Di Carlo P, Singh M, Ivanyi J, and Salerno A
- Subjects
- Adolescent, Chemoprevention, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay methods, Humans, Immunoglobulin G biosynthesis, Immunoglobulin G blood, Immunoglobulin G immunology, Immunoglobulin M biosynthesis, Immunoglobulin M blood, Tuberculosis blood, Tuberculosis immunology, Antitubercular Agents therapeutic use, Bacterial Proteins immunology, Chaperonins immunology, Immunoglobulin M immunology, Mycobacterium tuberculosis immunology, Tuberculin immunology, Tuberculosis prevention & control
- Abstract
Serum responses against Mycobacterium tuberculosis HSP16 were determined for children with tuberculosis (TB) and for healthy purified protein derivative (PPD)-positive and PPD-negative children. Immunoglobulin G (IgG) and IgM responses were higher for TB patients than for other groups. After chemotherapy, IgM and IgG responses decreased for TB patients and PPD-positive subjects. Monitoring of anti-M. tuberculosis HSP16 responses could assist in the management of pediatric TB.
- Published
- 2007
- Full Text
- View/download PDF
48. ESAT-6 peptide recognition by bovine CD8+ lymphocytes of naturally infected cows in herds from southern Italy.
- Author
-
Vitale F, Reale S, Petrotta E, Caracappa S, Barera A, La Manna MP, Macaluso P, Caccamo N, Dieli F, Vordermeier HM, Sireci G, and Salerno A
- Subjects
- Amino Acid Sequence, Animals, Antigens, Bacterial metabolism, Bacterial Proteins, CD8-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes microbiology, Cattle, Cells, Cultured, Epitopes, T-Lymphocyte immunology, Female, Interferon-gamma metabolism, Lymphocyte Activation immunology, Mice, Molecular Sequence Data, Sicily, Antigens, Bacterial immunology, CD8-Positive T-Lymphocytes immunology, Mycobacterium bovis immunology, Tuberculosis, Bovine immunology
- Abstract
The aim of this study was to define epitopes of Mycobacterium bovis from ESAT-6 (early secretory antigen of 6 kDa) recognized by CD8+ T lymphocytes from cows naturally infected with Mycobacterium bovis. We found that bovine CD8+ T cells recognized 10 out of 11 ESAT-6 peptides tested.
- Published
- 2006
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.