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IL-27 signaling is crucial for survival of mice infected with African trypanosomes via preventing lethal effects of CD4+ T cells and IFNγ

(2015) PLOS PATHOGENS. 11(7).
Author
Organization
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-gamma. 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-gamma, 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-gamma 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-gamma 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.
Keywords
TUMOR-NECROSIS-FACTOR, VARIANT SURFACE GLYCOPROTEIN, MEDIATES EARLY MORTALITY, NITRIC-OXIDE, CONGOLENSE INFECTIONS, INTERFERON-GAMMA, IMMUNOLOGICAL CLEARANCE, IMMUNE-RESPONSES, SUSCEPTIBLE MICE, BRUCEI INFECTION

Citation

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Chicago
Liu, Gongguan, Jinjun Xu, Hui Wu, Donglei Sun, Xiquan Zhang, Xiaoping Zhu, Stefan Magez, and Meiqing Shi. 2015. “IL-27 Signaling Is Crucial for Survival of Mice Infected with African Trypanosomes via Preventing Lethal Effects of CD4+ T Cells and IFNγ.” Plos Pathogens 11 (7).
APA
Liu, Gongguan, Xu, J., Wu, H., Sun, D., Zhang, X., Zhu, X., Magez, S., et al. (2015). IL-27 signaling is crucial for survival of mice infected with African trypanosomes via preventing lethal effects of CD4+ T cells and IFNγ. PLOS PATHOGENS, 11(7).
Vancouver
1.
Liu G, Xu J, Wu H, Sun D, Zhang X, Zhu X, et al. IL-27 signaling is crucial for survival of mice infected with African trypanosomes via preventing lethal effects of CD4+ T cells and IFNγ. PLOS PATHOGENS. 2015;11(7).
MLA
Liu, Gongguan, Jinjun Xu, Hui Wu, et al. “IL-27 Signaling Is Crucial for Survival of Mice Infected with African Trypanosomes via Preventing Lethal Effects of CD4+ T Cells and IFNγ.” PLOS PATHOGENS 11.7 (2015): n. pag. Print.
@article{8131472,
  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-gamma. 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-gamma, 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-gamma 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-gamma 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.},
  articleno    = {e1005065},
  author       = {Liu, Gongguan and Xu, Jinjun and Wu, Hui and Sun, Donglei and Zhang, Xiquan and Zhu, Xiaoping and Magez, Stefan and Shi, Meiqing},
  issn         = {1553-7366},
  journal      = {PLOS PATHOGENS},
  keyword      = {TUMOR-NECROSIS-FACTOR,VARIANT SURFACE GLYCOPROTEIN,MEDIATES EARLY MORTALITY,NITRIC-OXIDE,CONGOLENSE INFECTIONS,INTERFERON-GAMMA,IMMUNOLOGICAL CLEARANCE,IMMUNE-RESPONSES,SUSCEPTIBLE MICE,BRUCEI INFECTION},
  language     = {eng},
  number       = {7},
  pages        = {22},
  title        = {IL-27 signaling is crucial for survival of mice infected with African trypanosomes via preventing lethal effects of CD4+ T cells and IFN\ensuremath{\gamma}},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1005065},
  volume       = {11},
  year         = {2015},
}

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