B Cell/T Cell Interactions in Brucellosis

Project Summary/Abstract In humans, Brucella spp. can cause a lifelong, debilitating disease, with relapses of undulating fever and other complications even with antibiotic treatment. No vaccines are currently licensed to prevent human brucellosis, and mechanisms underlying the ability of Brucella to cause chronic infection are not well known. We have found B cells enhance susceptibility to Brucella infection by inhibiting CD4+ T cell-mediated immunity. In this proposal, we will test the hypothesis that B cell antigen presentation skews the CD4+ T cell response during brucellosis which impairs vaccine efficacy and contributes to chronicity of infection. In Aim #1 of this proposal we will investigate mechanisms by which B cell antigen presentation affects control of infection and modulates differentiation of CD4+ T cells into Th1, Th17, or regulatory T cells. In Aim #2 of this proposal, we determine how follicular interactions between B and CD4+ T cells affect antibody production and CD4+ T cell function and determine the relative contribution of IgG and IgM to immunity to infection. Collectively, our results will enhance our knowledge of the pathogenesis of chronic brucellosis and identify immunomodulatory strategies that can be incorporated into the rational design of brucellosis vaccines