25 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. 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
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
ANTIGENS ,T cells ,CYTOKINES ,IMMUNITY ,ZOONOSES ,IMMUNE response ,IMMUNOLOGICAL tolerance ,EUKARYOTIC cells - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
20. 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
21. 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
22. 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
23. 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
24. 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
25. 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
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.