IFN-γ deficiency alters splenic compartment cellular composition and Brucella distribution in a murine model of brucellosis

Abstract

Abstract Despite more than a century of research, brucellosis remains a major zoonotic threat with an estimated 500,000 human cases annually. No licensed vaccine exists to counter Brucella infection, leaving many who contract brucellosis with a chronic and debilitating disease. Immunohistochemistry studies have identified targets of Brucella infection in vivo. However, due to the low detection limit of this technique, high infectious doses of Brucella or immunodeficient mice are employed which likely changes the composition of the infected tissue. We and others observed increased splenic bacterial burden and susceptibility to Brucella infection in mice deficient in IFN-γ. Therefore, to determine if IFN-γ changes splenic composition and cellular distribution of Brucella, we performed live cell sorting on spleens from Brucella- infected wild-type (WT) and IFN-γ−/− mice. Spleens from Brucella-infected IFN-γ−/− mice exhibited a lower proportion of B cells and an increased proportion of neutrophils and macrophages compared to WT mice. Interestingly, 90% of intracellular, viable Brucella from WT spleens during chronic infection was in B cells while the proportion of bacterial burden was similar amongst B cells, macrophages, and neutrophils within IFN-γ−/− spleens. In studies using B-cell deficient (μMT−/−) mice challenged with Brucella, we found significantly decreased bacterial burden in μMT−/− spleens compared to WT mice despite similar levels recovered from the joint between both groups. Collectively, these findings indicate that IFN-γ deficiency alters the distribution of cells within the splenic compartment and that B cells enhance Brucella burden in the spleen.