Title | IL-27 Signaling Is Crucial for Survival of Mice Infected with African Trypanosomes via Preventing Lethal Effects of CD4+ T Cells and IFN-γ. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Liu, G., J. Xu, H. Wu, D. Sun, X. Zhang, X. Zhu, S. Magez, and M. Shi |
Journal | PLoS Pathog |
Volume | 11 |
Issue | 7 |
Pagination | e1005065 |
Date Published | 2015 Jul |
ISSN | 1553-7374 |
Keywords | Animals, CD4-Positive T-Lymphocytes, Cell Death, Interferon-gamma, Interleukins, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction, Trypanosoma, Trypanosomiasis |
Abstract | African trypanosomes are extracellular protozoan parasites causing a chronic debilitating disease associated with a persistent inflammatory response. Maintaining the balance of the inflammatory response via downregulation of activation of M1-type myeloid cells was previously shown to be crucial to allow prolonged survival. Here we demonstrate that infection with African trypanosomes of IL-27 receptor-deficient (IL-27R-/-) mice results in severe liver immunopathology and dramatically reduced survival as compared to wild-type mice. This coincides with the development of an exacerbated Th1-mediated immune response with overactivation of CD4+ T cells and strongly enhanced production of inflammatory cytokines including IFN-γ. What is important is that IL-10 production was not impaired in infected IL-27R-/- mice. Depletion of CD4+ T cells in infected IL-27R-/- mice resulted in a dramatically reduced production of IFN-γ, preventing the early mortality of infected IL-27R-/- mice. This was accompanied by a significantly reduced inflammatory response and a major amelioration of liver pathology. These results could be mimicked by treating IL-27R-/- mice with a neutralizing anti-IFN-γ antibody. Thus, our data identify IL-27 signaling as a novel pathway to prevent early mortality via inhibiting hyperactivation of CD4+ Th1 cells and their excessive secretion of IFN-γ during infection with African trypanosomes. These data are the first to demonstrate the essential role of IL-27 signaling in regulating immune responses to extracellular protozoan infections. |
DOI | 10.1371/journal.ppat.1005065 |
Alternate Journal | PLoS Pathog. |
PubMed ID | 26222157 |
PubMed Central ID | PMC4519326 |
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