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- W4313385194 abstract "Abstract Tuberculosis (TB), caused by M. tuberculosis (Mtb), continues to be a global health problem. Lung granulomas, organized structures of host immune cells to contain Mtb, are the pathologic hallmark of TB. T cell cytokines play a major role in containment of Mtb infection within these granulomas. While the importance of pro-inflammatory cytokines IFN-γ and TNF in controlling Mtb infections has been established, the effects of immunomodulatory cytokines, such as IL-10, in Mtb infections are less well understood. We used cynomolgus macaques, a non-human primate (NHP) model that recapitulates human TB to investigate the role of IL-10 early in Mtb infection. Preliminary ex vivo studies of excised lung granulomas from Mtb-infected NHPs suggested IL-10 may be downregulating IL-2 cytokine production in TB lung granulomas. To further examine the role of IL-10, a cross-reactive, rhesus recombinant anti-IL-10 antibody was used to neutralize IL-10 in vivo in NHPs prior to and during the course of Mtb infection. Peripheral cytokine responses in the presence of IL-10 neutralization were analyzed serially by flow cytometry of peripheral blood mononuclear cells. Disease progression was monitored by PET-CT scans, and local immune responses in the granulomas assessed at necropsy. Our data indicate transient differences in inflammation early in infection between anti-IL-10-treated and control monkeys. Surprisingly, there was less inflammation in granulomas from IL-10 neutralized animals at 3–4 weeks post-infection, compared to control animals. Overall, this unique dataset provides important insight into the contribution of IL-10 to the necessary immunological balance for controlled bacterial burden and disease pathology in Mtb infections." @default.
- W4313385194 created "2023-01-06" @default.
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- W4313385194 date "2017-05-01" @default.
- W4313385194 modified "2023-10-17" @default.
- W4313385194 title "The role of IL-10 during early <i>M. tuberculosis</i> infection in a non-human primate model" @default.
- W4313385194 doi "https://doi.org/10.4049/jimmunol.198.supp.123.5" @default.
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