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

作者：Mariana N. Xavier, Maria G. Winter, Alanna M. Spees, Kim Nguyen, Vidya Atluri, Teane M. A. Silva, Andreas J. Bäumler, Werner Müller, Renato L. Santos, Renée M. Tsolis · 发表于：PLoS Pathogens · 年份：2013 · DOI：10.1371/journal.ppat.1003454 · 被引用次数：109 · 研究领域：Brucella: diagnosis, epidemiology, treatment、Galectins and Cancer Biology、Atherosclerosis and Cardiovascular Diseases

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.