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Background: Emerging data has suggested that Tregs, Th17, Th1 and Th2 are correlated with early immune mechanisms by controlling Plasmodium infection. Plasmodium infection appeared to impair the antigen presentation and maturation of DCs, leading to attenuation of specific cellular immune response ultimately. Hence, in this study, we aim to evaluate the relevance between DCs and Tregs/Th17 populations in the process and outcomes of infection with Plasmodium yoelii 17XL (P.y17XL).Methods: DCs detection/analysis dynamically was performed by Tregs depletion or Th17 neutralization in P.y17XL infected BALB/c mice via flow cytometry. Then the levels of cytokines production were detected using enzyme-linked mmunosorbent assay (ELISA).Results: Our results indicated that Tregs depletion or Th17 neutralization in BALB/c mice infected with P.y17XL significantly up-regulated the percentages of mDC and pDC, increased the expressions of major histocompatibility complex (MHC) class II, CD80, CD86 on DCs and the levels of IL-10/IL-12 secreted by DCs, indicating that abnormal amplification of Tregs or Th17 may damage the maturation and function of DCs during the early stage of malaria infection. Interestingly, we also found that the abnormal amplification of Th17, as well as Tregs, could inhibit the maturation of DCs.Conclusions: Tregs skewing or Th17 amplification during the early stage of malaria infection may inhibit the maturation and function of DCs by modifying the subsets of DCs, expressions of surface molecules on DCs and secretion mode of cytokines. [ABSTRACT FROM AUTHOR]

Background: Treponema pallidum (T. pallidum) infection evokes significant immune responses, resulting in tissue damage. The immune mechanism underlying T. pallidum infection is still unclear, although microRNAs (miRNAs) have been shown to influence immune cell function and, consequently, the generation of antibody responses during other microbe infections. However, these mechanisms are unknown for T. pallidum.Methods: In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy individuals, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. miRNAs were profiled from the peripheral blood of patients obtained at the time of serological diagnosis. Then, both the target sequence analysis of these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for microRNA analysis.Results: A total of 74 differentially regulated miRNAs were identified. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant differences in the serofast and serologically cured states (P < 0.05). One miRNA (hsa-miR-195-5p) showed significant differences between untreated patients and healthy individuals.Conclusions: This is the first study of miRNA expression differences in peripheral blood mononuclear cells (PBMCs) in different stages of T. pallium infection. Our study suggests that the combination of three miRNAs has great potential to serve as a non-invasive biomarker of T. pallium infections, which will facilitate better diagnosis and treatment of T. pallium infections. [ABSTRACT FROM AUTHOR]

Background: Chronic Chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. Previous results have shown that the immune response plays an important role, although no all mechanisms are understood. Immunoregulatory mechanisms such as apoptosis are important for the control of Chagas disease, possibly affecting the morbidity in chronic clinical forms. Apoptosis has been suggested to be an important mechanism of cellular response during T. cruzi infection. We aimed to further understand the putative role of apoptosis in Chagas disease and its relation to the clinical forms of the disease.Methods: Apoptosis of lymphocytes, under antigenic stimuli (soluble T. cruzi antigens - TcAg) where compared to that of non-stimulated cells. Apoptosis was evaluated using the expression of annexin and caspase 3(+) by T cells and the percentage of cells positive evaluated by flow cytometry. In addition activation and T cell markers were used for the identification of TCD4(+) and TCD8(+) subpopulations. The presence of intracellular and plasma cytokines were also evaluated. Analysis of the activation status of the peripheral blood cells showed that patients with Chagas disease presented higher levels of activation determined by the expression of activation markers, after TcAg stimulation. PCR array were used to evaluate the contribution of this mechanism in specific cell populations from patients with different clinical forms of human Chagas disease.Results: Our results showed a reduced proliferative response associated a high expression of T CD4(+)CD62L(-) cells in CARD patients when compared with IND group and NI individuals. We also observed that both groups of patients presented a significant increase of CD4(+) and CD8(+) T cell subsets in undergoing apoptosis after in vitro stimulation with T. cruzi antigens. In CARD patients, both CD4(+) and CD8(+) T cells expressing TNF-α were highly susceptible to undergo apoptosis after in vitro stimulation. Interestingly, the in vitro TcAg stimulation increased considerably the expression of cell death TNF/TNFR superfamily and Caspase family receptors genes in CARD patients.Conclusions: Taken together, our results suggest that apoptosis may be an important mechanism for the control of morbidity in T. cruzi infection by modulating the expression of apoptosis genes, the cytokine environment and/or killing of effector cells. [ABSTRACT FROM AUTHOR]

Background: In addition to their antimicrobial activity, antibiotics modulate cellular host defence. Granulocyte-colony stimulating factor (G-CSF) is also a well known immunomodulator; however little is known about the interactions of G-CSF with antibiotics. We investigated in septic rats the effects of two antibiotic combinations with G-CSF. Methods: In two clinic modelling randomised trials (CMRTs), male Wistar rats were anesthetized, given antibiotic prophylaxis, had a laparotomy with peritoneal contamination and infection (PCI), and were randomly assigned (n = 18 rats/group) to: 1) PCI only; 2) PCI+antibiotic; and, 3) PCI+antibiotic+G-CSF prophylaxis (20 µg/kg, three times). This sequence was conducted first with 10 mg/kg coamoxiclav, and then with ceftriaxone/metronidazole (Cef/met, 10/3 mg/kg). In additional animals, the blood cell count, migration and superoxide production of PMNs, systemic TNF-α and liver cytokine mRNA expression levels were determined. Results: Only the combination coamoxiclav plus G-CSF improved the survival rate (82 vs. 44%, p < 0.001). Improved survival with this combination was accompanied by normalised antimicrobial PMN migratory activity and superoxide production, along with normalised systemic TNF-α levels and a reduced expression of TNF-α and IL-1 in the liver. Conclusion: There are substantial differences in the interaction of antibiotics with G-CSF. Therefore, the selection of the antibiotic for combination with G-CSF in sepsis treatment should be guided not only by the bacteria to be eliminated, but also by the effects on antimicrobial functions of PMNs and the cytokine response. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic fever with renal syndrome (HFRS) caused by pathogenic hantaviruses in Europe and Asia is often characterized by acute kidney injury (AKI) with massive proteinuria. Renal filtration depends on the integrity of epithelial and endothelial monolayers in the tubular and glomerular apparatus. Tubular and glomerular cells represent target cells of hantavirus infection. However, the detailed mechanisms of renal impairment induced by hantaviruses are not well understood.Methods: We analyzed the cellular consequences of hantavirus infection by measuring adhesion and migration capacity of human renal cells infected with Puumala (PUUV) or Hantaan (HTNV) virus. The impact of hantaviral nucleocapsid proteins (N proteins) on motility was examined by transfection of podocytes.Results: Infection of kidney cells with hantavirus species PUUV and HTNV causes a significant reduction of migration capacity. The impaired motility depends on viral replication and transfection of podocytes with N protein of PUUV or HTNV reveals that the expression of N protein alone is sufficient to deteriorate podocyte function. The cellular effects are more pronounced for the more pathogenic HTNV than for PUUV that causes a milder form of HFRS.Conclusions: The direct impairment of migration capacity of renal cells by hantaviral N proteins may contribute substantially to proteinuria observed in the clinical picture of hantavirus infection. [ABSTRACT FROM AUTHOR]