ABSTRACT
Background: Tolerance induces a regulated immune response to infection. We hypothesized that tolerance induction modulated profile of T regulatory cell (Treg) and T lymphocyte 17 (Th17) cells and is related cytokine released in septic animals. Methods: Male black C57/6 mice received subcutaneous (s.c.) injections of lipopolysaccharide (LPS) (1 mg/kg) for 5 days, on day 8th was made cecal ligation and puncture (CLP). Blood and spleen tissue were collected for cell analysis and cytokines measurements. Results: Cytokines (interleukin 2 (IL-2), interleukin (IL-6), transforming growth factor ß (TGF-ß) and interferon γ (INF-γ)) related to Treg and Th17 stimulation were elevated in the spleen of tolerant animals compared to sham. Treg and Th17 lymphocytes showed an increased amount in blood (Treg: 920 ± 84 cells vs. 1946 ± 65 cells, sham vs. tolerant; Th17:38321± 1954 cells vs. 43526 ± 7623 cells, sham vs. tolerant) and spleen (Treg: 5947 ± 273 cells vs. 16521 ± 486 cells, sham vs. tolerant; Th17: 26543 ± 2944 cells vs. 64567 ± 5523 cells, sham vs. tolerant). Treg (135±23 cells) and Th17 (1590 ± 256 cells) cells were reduced in blood of septic animals compared to sham, while CLP tolerant animals presented an increasing number of these cells. Lymphocyte Th17IL6+ were elevated in tolerant and CLP tolerant animals in the blood compared to sham. Conclusion: LPS tolerance was associated with increasing population of Treg and Th17. LPS tolerance reduces the hyper inflammatory response with immunoregulation exerted by Treg and Th17 cells protecting from septic damage.
ABSTRACT
Visceral Leishmaniasis (VL) is caused by intracellular parasites of the genus Leishmania that affect humans and several animal species. Dogs are one of the main urban reservoirs of the parasite and play a central role in the transmission cycle to humans via sandflies. Studies concerning the immune response in dogs with VL have demonstrated that protective immunity is associated with cellular immune response, while disease progression is associated with humoral response and IL-10 and TGF-ß production. The study aimed to evaluate IL-10 and TGF-ß production by regulatory T (Treg) cells in the blood and spleen of dogs naturally infected by Leishmania spp. and correlate this with parasite load. Five healthy dogs and 29 dogs with proven infection were selected for the study group. Real-time PCR was used to quantify parasite load and confirm infection by Leishmania spp. Treg cells producing IL-10 and TGF-ß were quantified using flow cytometry. An increase in IL-10 production by Treg cells was verified in the spleen of dogs naturally infected by Leishmania spp. Concurrently, a decrease in the total number of T cells in these dogs was verified compared with healthy dogs. No association was determined between parasite load and the percentage of spleen Treg cells producing IL-10 and TGF-ß. These findings suggest that Treg cells are an important source of IL-10 in the spleen, participating in immune response modulation, while the reduced percentage of these cells in infected dogs could be attributed to persistent immune activation.
