B Cell/T Cell Interactions in Brucellosis

项目摘要/摘要 人类布鲁氏菌属(Brucella spp.)会导致终生衰弱的疾病，并反复出现波状发烧和 即使使用抗生素治疗也会出现其他并发症。目前还没有获得许可的疫苗来预防人类 布鲁氏菌病以及布鲁氏菌引起慢性感染的潜在机制还不是很清楚。我们 已经发现B细胞通过抑制CD4+T细胞介导的免疫来增强对布鲁氏菌感染的易感性。在……里面 在这项提议中，我们将检验B细胞抗原呈递会扭曲CD4+T细胞反应的假设 布鲁氏菌病，削弱疫苗效力，并导致感染的慢性化。在本提案的目标1中 我们将研究B细胞抗原提呈影响感染控制和调节的机制 将CD4+T细胞分化为Th1、Th17或调节性T细胞在本提案的目标2中，我们确定如何 B和CD4+T细胞之间的滤泡相互作用影响抗体的产生和CD4+T细胞的功能 确定免疫球蛋白和免疫球蛋白M对感染免疫的相对贡献。总体而言，我们的结果将提高 我们对慢性布鲁氏菌病发病机制的了解，并确定可以 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