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CD4+ T Cell-derived IL-10 Promotes Brucella abortus Persistence via Modulation of Macrophage Function
Authors:Mariana N. Xavier  Maria G. Winter  Alanna M. Spees  Kim Nguyen  Vidya L. Atluri  Teane M. A. Silva  Andreas J. B?umler  Werner Müller  Renato L. Santos  Renée M. Tsolis
Affiliation:1. Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, United States of America.; 2. Departamento de Clínica e Cirurgia Veterinárias, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.; 3. Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.; Yale University School of Medicine, United States of America,
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.
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