IRF-5 Promotes Cell Death in CD4 T Cells during Chronic Infection

Cell Rep. 2018 Jul 31;24(5):1163-1175. doi: 10.1016/j.celrep.2018.06.107.

Abstract

The transcription factor interferon regulatory factor 5 (IRF-5) plays an important function in innate immunity and in initiating pro-inflammatory responses against pathogens. IRF-5 is constitutively expressed in several cell types, including plasmacytoid dendritic cells, monocytes, and B cells. We have previously reported that IRF-5 is also expressed in T cells during infection. The role of IRF-5 in T cells is yet unknown. Here, we demonstrate that IRF-5 is increasingly expressed in interferon (IFN)-γ+ CD4 T cells over the course of L. donovani infection. This transcription factor is induced by apoptotic material via Toll-like receptor 7 (TLR7) and promotes the expression of death receptor 5 (DR5). IRF-5 activation sensitizes CD4 T cells to cell death. Because tissue disruption and chronic inflammation are common characteristics of persistent infections, activation of IRF-5 in CD4 T cells may represent a common pathway that leads to suppression of protective CD4 T cell responses, favoring the establishment of chronic infection.

Keywords: CD4 T cells; DR5; IRF-5; Leishmania; TLR7; cell death; chronic infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Female
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism*
  • Leishmaniasis, Visceral / metabolism*
  • Male
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Toll-Like Receptor 7 / metabolism

Substances

  • Interferon Regulatory Factors
  • Irf5 protein, mouse
  • Membrane Glycoproteins
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Tlr7 protein, mouse
  • Tnfrsf10b protein, mouse
  • Toll-Like Receptor 7

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