T cell-derived IL-10 promotes Brucella abortus persistence via modulation of macrophage function

• Published in: PLoS pathogens Vol. 9; no. 6
• Main Authors: Xavier, Mariana N, Winter, Maria G, Spees, Alanna M, Atluri, Vidya L, Silva, Teane M.A, Baumler, Andreas J, Muller, Werner, Santos, Renato L, Tsolis, Renee M
• Format: Journal Article
• Language: English
• Published: Public Library of Science 01.06.2013
• Subjects: Health aspects; Host-parasite relationships; Interleukin-10; Macrophages; Physiological aspects; T cells; United States
• ISSN: 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003454

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.sup.+][CD25.sup.+] 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-κB 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.sup.+][CD4.sup.+] 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.