CD4+ T Cell-derived IL-10 Promotes Brucella abortus Persistence via Modulation of Macrophage Function

Mariana N. Xavier, Maria G. Winter, Alanna M. Spees, Kim Nguyen, Vidya L. Atluri, Teane M A Silva, Andreas J Baumler, Werner Müller, Renato L. Santos, Renee M Tsolis

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Evasion of host immune responses is a prerequisite for chronic bacterial diseases; however, the underlying mechanisms are not fully understood. Here, we show that the persistent intracellular pathogen Brucella abortus prevents immune activation of macrophages by inducing CD4+CD25+ T cells to produce the anti-inflammatory cytokine interleukin-10 (IL-10) early during infection. IL-10 receptor (IL-10R) blockage in macrophages resulted in significantly higher NF-kB activation as well as decreased bacterial intracellular survival associated with an inability of B. abortus to escape the late endosome compartment in vitro. Moreover, either a lack of IL-10 production by T cells or a lack of macrophage responsiveness to this cytokine resulted in an increased ability of mice to control B. abortus infection, while inducing elevated production of pro-inflammatory cytokines, which led to severe pathology in liver and spleen of infected mice. Collectively, our results suggest that early IL-10 production by CD25+CD4+ T cells modulates macrophage function and contributes to an initial balance between pro-inflammatory and anti-inflammatory cytokines that is beneficial to the pathogen, thereby promoting enhanced bacterial survival and persistent infection.

Original languageEnglish (US)
Article numbere1003454
JournalPLoS Pathogens
Volume9
Issue number6
DOIs
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

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    Xavier, M. N., Winter, M. G., Spees, A. M., Nguyen, K., Atluri, V. L., Silva, T. M. A., Baumler, A. J., Müller, W., Santos, R. L., & Tsolis, R. M. (2013). CD4+ T Cell-derived IL-10 Promotes Brucella abortus Persistence via Modulation of Macrophage Function. PLoS Pathogens, 9(6), [e1003454]. https://doi.org/10.1371/journal.ppat.1003454