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

PLoS Pathogens

Werner Müller¹  Maria G. Winter¹  Teane M. A. Silva²  Mariana N. Xavier²  Andreas J. Bäumler²  Renato L. Santos²  Vidya L. Atluri²  Alanna M. Spees²  Kim Nguyen²  Renée M. Tsolis³ 

[1] Departamento de Clínica e Cirurgia Veterinárias, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America;Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom

关键词: Macrophages;    T cells;    Brucella;    Spleen;    Cytokines;    Infectious disease control;    Neutrophils;    Immune response;   

DOI  :  10.1371/journal.ppat.1003454

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY