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CD4+ T Cell-derived IL-10 Promotes Brucella abortus Persistence via Modulation of Macrophage Function
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نویسنده
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xavier m.n. ,winter m.g. ,spees a.m. ,nguyen k. ,atluri v.l. ,silva t.m.a. ,bäumler a.j. ,müller w. ,santos r.l. ,tsolis r.m.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 6
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چکیده
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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. © 2013 xavier et al.
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آدرس
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department of medical microbiology and immunology,school of medicine,university of california at davis,davis,ca,united states,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,ca, United States, department of medical microbiology and immunology,school of medicine,university of california at davis,davis,ca, United States, department of medical microbiology and immunology,school of medicine,university of california at davis,davis,ca, United States, department of medical microbiology and immunology,school of medicine,university of california at davis,davis,ca, United States, department of medical microbiology and immunology,school of medicine,university of california at davis,davis,ca,united states,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,ca, United States, faculty of life sciences,university of manchester,manchester, United Kingdom, 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,ca, United States
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Authors
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