B Cell/T Cell Interactions in Brucellosis

项目总结/摘要 在人类中，布鲁氏菌属（Brucella spp.）可能导致终身衰弱的疾病，反复出现波动性发热， 其他并发症，甚至抗生素治疗。目前没有疫苗被许可用于预防人类 布鲁氏菌病和布鲁氏菌引起慢性感染的潜在机制尚不清楚。我们 已经发现B细胞通过抑制CD 4 + T细胞介导的免疫增强对布鲁氏菌感染的易感性。在 在这个提议中，我们将检验B细胞抗原呈递在免疫过程中扭曲CD 4 + T细胞应答的假设。 布鲁氏菌病，它损害疫苗效力并导致感染慢性化。在本提案的目标#1中 我们将研究B细胞抗原呈递影响感染控制和调节 CD 4 + T细胞分化为Th 1、Th 17或调节性T细胞。在本提案的目标#2中，我们确定如何 B和CD 4 + T细胞之间的滤泡相互作用影响抗体产生和CD 4 + T细胞功能， 确定IgG和IgM对感染免疫的相对贡献。总的来说，我们的成果将提高 我们对慢性布鲁氏菌病发病机制的认识，并确定免疫调节策略， 纳入布鲁氏菌病疫苗的合理设计

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