B Cell/T Cell Interactions in Brucellosis

布鲁氏菌病中 B 细胞/T 细胞的相互作用

基本信息

批准号：
10512061
负责人：
Jerod Skyberg
金额：
$ 52.02万
依托单位：
UNIVERSITY OF MISSOURI-COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-11-18 至 2025-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10512061
关键词：
Adoptive Transfer Affect Animals Antibiotic Therapy Antibodies Antibody Formation Antigen Presentation Antigen-Presenting Cells Antigens B-Cell Antigen Receptor B-Lymphocytes BLR1 gene Bone Marrow Brucella Brucella Vaccine Brucellosis CD4 Positive T Lymphocytes Cell Communication Cell physiology Cellular Immunity Chimera organism Chronic Data Development Disease FOXP3 gene Fever Future Goals Homing Human Immunity Immunoglobulin Class Switching Immunoglobulin G Immunoglobulin M Impairment Infection Infection Control Interleukin-10 Knowledge Licensing Mediating Mus Mutant Strains Mice Pathogenesis Phenotype Predisposition Production Public Health Receptor Signaling Regulatory T-Lymphocyte Resistance Role Signal Transduction Sterility T cell response T-Cell Activation T-Cell Development T-Lymphocyte Testing Vaccines Zoonoses chronic infection conditional mutant effector T cell humoral immunity deficiency immunomodulatory strategy improved in vivo neglect preservation prevent rational design uptake vaccine efficacy

项目摘要

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

项目摘要/摘要在人类中，布鲁氏菌。会引起终生，使人衰弱的疾病，并带有起伏的发烧和即使接受抗生素治疗，其他并发症也是如此。目前没有疫苗可以预防人类布鲁氏菌病以及布鲁氏菌引起慢性感染能力的基础的机制尚不清楚。我们发现B细胞通过抑制CD4+ T细胞介导的免疫力来增强对布鲁氏菌感染的敏感性。在该提案，我们将检验以下假设：B细胞抗原表现偏向CD4+ T细胞反应布鲁塞病损害疫苗功效并导致感染的慢性性。在本提案的目标＃1中我们将研究B细胞抗原表现影响感染和调节的控制的机制 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 B和CD4+ T细胞之间的卵泡相互作用会影响抗体的产生和CD4+ T细胞功能以及确定IgG和IgM对免疫对感染的相对贡献。总体而言，我们的结果将增强我们对慢性布鲁氏菌病的发病机理的了解，并确定可以是的免疫调节策略纳入布鲁氏菌病疫苗的合理设计