IL-27 Signaling Is Crucial for Survival of Mice Infected with African Trypanosomes via Preventing Lethal Effects of CD4 T Cells and IFN-γ

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Infection with extracellular protozoan parasites, African trypanosomes, is characterized by a persistent inflammatory immune response. It has been recently shown that maintaining the balance of the inflammatory responses via dampening M1-type myeloid cell activation is critical to guarantee control of the parasites and survival of the host. In this study, we demonstrated that IL-27 receptor-deficient (IL-27R-/-) mice infected with African trypanosomes developed an excessive inflammatory response and severe liver immunopathology, resulting in dramatically reduced survival, as compared to infected wild-type mice. The early mortality of infected IL-27R-/ -⁠ mice was correlated with significantly elevated secretions of inflammatory cytokines, particularly IFN-γ, and enhanced activation of CD4+ Th1 cells. Importantly, IL-10 production was not impaired in infected IL-27R-/ -⁠ mice. Either depletion of CD4+ T cells, resulting in a dramatically reduced secretion of IFN-γ, or neutralization of IFN-γ, prevented the early mortality of infected IL-27R-/ -⁠ mice with a significantly reduced inflammatory response and a major amelioration of the liver pathology. Thus, our data identify IL-27 signaling as a novel pathway to prevent the early mortality via inhibiting hyperactivation of CD4+ Th1 cells and their excessive secretions of IFN-γ during experimental infection with extracellular protozoan parasites African trypanosomes.

Vyšlo v časopise: IL-27 Signaling Is Crucial for Survival of Mice Infected with African Trypanosomes via Preventing Lethal Effects of CD4 T Cells and IFN-γ. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005065
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005065

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