Abstract
IL-10 is a cytokine that regulates the balance between pathogen clearance and immunopathology. Brucella abortus is an intracellular bacterium that causes chronic disease in humans and domestic animals. Here we evaluated the contribution of IL-10 in host immune response and pathology during B. abortus infection. To assess the role of IL-10 in vivo, IL-10 knockout (KO) or 129 Sv/Ev (wild-type) mice were infected with B. abortus and the number of viable bacteria from the spleen was determined at 1, 2, 3, 6 and 14-weeks postinfection. IL-10 KO mice showed reduced bacterial loads in the spleen when compared to wild-type mice during all time points studied. Additionally, at 14-weeks postinfection IL-10 KO mice had totally cleared the infection. This clearance was preceded by an enhanced IFN-γ, TNF-α and IL-17 responses in both the serum and the spleen of IL-10 KO mice. Additionally, dendritic cells from infected IL-10 KO mice produced elevated levels of IL-12 and TNF-α compared to wild-type animals. Histopathology analysis was performed and both KO and wild-type mice developed multifocal granulomas and necrosis in the liver. However, at six-weeks postinfection reduced numbers of granulomas was detected in IL-10 KO mice compared to wild-type animals. This reduced liver pathology at later stage of infection was accompanied by increased numbers of CD4+CD25+foxp3+ T cells and expression of TGF-β in IL-10 KO splenocytes. Taken together, our findings demonstrate that IL-10 modulates the proinflammatory immune response to B. abortus infection and the lack of IL-10 increases resistance to Brucella infection.
Highlights
In general bacterial infections induced by Gram-negative microorganisms are associated with an acute inflammatory reaction, which represents the principal local defense against spread of the infection [1]
To investigate whether B. abortus induces IL-10, BMDC or splenocytes were exposed to bacteria and IL-10 was measured
Fluorescence-activated Cell Sorter (FACS) analysis revealed that CD4+ T cells, macrophages and dendritic cells are the major IL-10 producers within splenocytes (Figure 1C)
Summary
In general bacterial infections induced by Gram-negative microorganisms are associated with an acute inflammatory reaction, which represents the principal local defense against spread of the infection [1]. Brucella abortus is a Gram-negative, facultative intracellular coccobacillus which causes brucellosis, a chronic inflammatory disease, in humans and in cattle. The protective response against B. abortus infection requires CD4+ and CD8+ T lymphocytes, Th1-type cytokines such as interferon-gamma (IFN-c) and tumor necrosis factor (TNF-a), and activated macrophages and dendritic cells [9,10]. IFN-c was demonstrated to be a critical cytokine for host control of Brucella infection [9,11]. Bacterial recognition by macrophages and dendritic cells activates intracellular signaling pathways that culminate in the induction of inflammatory cytokines, chemokines, interferons and upregulation of co-stimulatory molecules. IL-10 production represents a potent autoregulatory feedback loop that protects against excessive inflammation and potential tissue destruction during proinflammatory Th1-driven immune responses in infections [17]
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