IFN-g counteracts YopH mediated immune evasion in Yersinia enterocolitica infection in mice

Background: Yersinia outer protein (Yop) H is a secreted virulence factor of Yersinia enterocolitica which inhibits phagocytosis of Y. enterocolitica and promotes virulence of Y. enterocolitica (Ye) in mice. The aim of this study was to address whether and how YopH affects the innate immune response against Ye in mice. Results: For this purpose mice were infected with wild type Ye (pYV+) or a YopH-deficient Ye mutant strain (DyopH). CD11b+ cells were isolated from infected spleen and subjected to gene expression analysis using microarrays. Despite attenuation of DyopH in vivo, by variation of infection doses we were able to achieve conditions that allow comparison of gene expression in pYV+ and DyopH infections at either comparable infection courses or splenic bacterial burden. Gene expression analysis provided evidence that expression levels of several immune response genes including IFN-g and IL-6 are high after pYV+ infection but low after sublethal DyopH infection. In line with these findings, infection of IFN-gR-/- and IL-6-/- mice with pYV+ or DyopH revealed that these cytokines are dispensable for control of DyopH, but not pYV+ infection. Consistently, in bacteria killing assays with BMM in vitro, stimulation of BMM with IFN-g is required for killing of pYV+ but not DyopH. Conclusion: In conclusion, this data suggest that IFN-g counteracts YopH-mediated virulence mechanisms of Ye which in Ye wild type infection contribute to evasion of the innate immune response including killing by macrophages. Keywords: Comparison of gene expression due to bacterial virulence factors In this study microarray analyses were performed to define differences in gene expression of cells associated with innate immune response (CD11b+ cells) after infection of mice with a sublethal and lethal infection with wildtype Yersinia enterocolitica compared to uninfected mice. In addition, we wanted to investigate whether differences in gene expression can be defined which are due to the virulence factor YopH. Moroeover, we were interested whether gene expression pattern of sublethal and lethal infected mice are different. Allover all five samples were compared. Number of replicates 1.