Interleukin 10 suppresses lysosome-mediated killing of Brucella abortus in cultured macrophages [Immunology]

Brucella abortus is a Gram-negative zoonotic pathogen for which there is no 100% effective vaccine. Phagosomes in B. abortus–infected cells fail to mature, allowing the pathogen to survive and proliferate. Interleukin 10 (IL10) promotes B. abortus persistence in macrophages by mechanisms that are not fully understood. In this study, we investigated the regulatory role of IL10 in the immune response to B. abortus infection. B. abortus–infected macrophages were treated with either IL10 siRNA or recombinant IL10 (rIL10), and the expression of phagolysosome- or inflammation-related genes was evaluated by qRT-PCR and Western blotting. Phagolysosome fusion was monitored by fluorescence microscopy. We found that the synthesis of several membrane-trafficking regulators and lysosomal enzymes was suppressed by IL10 during infection, resulting in a significant increase in the recruitment of hydrolytic enzymes by Brucella-containing phagosomes (BCPs) when IL10 signaling was blocked. Moreover, blocking IL10 signaling also enhanced proinflammatory cytokine production. Finally, concomitant treatment with STAT3 siRNA significantly reduced the suppression of proinflammatory brucellacidal activity but not phagolysosome fusion by rIL10. Thus, our data provide the first evidence that clearly indicates the suppressive role of IL10 on phagolysosome fusion and inflammation in response to B. abortus infection through two distinct mechanisms, STAT3-independent and -dependent pathways, respectively, in murine macrophages.

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