Article

IL-10 Restrains IL-17 to Limit Lung Pathology Characteristics following Pulmonary Infection with Francisella tularensis Live Vaccine Strain.

Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
American Journal Of Pathology (Impact Factor: 4.6). 09/2013; DOI: 10.1016/j.ajpath.2013.07.008
Source: PubMed

ABSTRACT IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10-deficient mice (Il10(-/-)), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10(-/-)-infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain.

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    ABSTRACT: Francisella tularensis, a facultative intracellular Gram-negative bacterium, causes the illness tularemia. The infection of mice with live vaccine strain is considered to be a model of human tularemia. F. tularensis infects predominantly such phagocytic cells as macrophages or neutrophils, but it also infects non-phagocytic hepatocytes, epithelial cells, and murine and human B cell lines. Based on work with the murine tularemia model, we report here that F. tularensis LVS infects peritoneal CD19+ cells – exclusively B-1a cells – early after intraperitoneal infection in vivo. The peritoneal and consequently spleen CD19+ cells are activated by the F. tularensis LVS infection to express the activation markers from MHC class II, CD25, CD54, CD69, and the co-stimulatory molecules CD80 and CD86. As early as 12 h post-infection, the peritoneal CD19+ cells produce IFN-γ, IL-1β, IL-4, IL-6, IL-12, IL-17, IL-23, and TNF-α. The spleen CD19+ cells respond to infection with some delay. Moreover, the F. tularensis infected A20 B cell line activates CD3+ spleen cells isolated from naïve mice. Thus, the data presented here suggest that B cells have all the attributes to actively participate in the induction and regulation of the adaptive immune response during early stages of F. tularensis infection.
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