Vanin-1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection

Q fever is caused by Coxiella burnetti, a bacterium that survives in M phi. Vanin-1 is a membrane-anchored pantetheinase that controls tissue inflammation. Consequently, Vanin-1-deficient mice represent a unique mouse model in which stress-induced inflammation is limited by the reaction of resident tissue cells. To investigate the contribution of host tissues in the control of a bacterial infection, we infected Vanin-1-deficient mice with C burnetii. Mortality and morbidity of mice were not affected. The lack of Vanin-1 had no effect on C. burnetti clearance but decreased the formation of granulomas in spleen and liver. Granuloma formation depends upon M phi recruitment and activation in these tissues. Whereas the former was slightly impaired in mutant mice, the lack of Vanin-1 significantly affected the activation pattern of BM-derived M(D stimulated by C. burnetti. While their microbicidal activity against C. burnetii was moderately impaired, they exhibited decreased inducible nitric oxide synthase (NOS) and MCP-1 gene expression, and increased IL-10 and arginase expression. In liver from mutant mice, increased arginase expression and decreased expression of MCP-1 and NOS were reminiscent of M(P data. These results suggest a role of Vanin-1 in granuloma formation in response to C. burnetti by skewing M phi activation toward an M2 program.