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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

项目概要/摘要在人类中，布鲁氏菌属。可能会导致终生的、使人衰弱的疾病，伴有反复出现的波动性发烧和即使使用抗生素治疗也会出现其他并发症。目前还没有疫苗被批准用于预防人类布鲁氏菌病以及布鲁氏菌引起慢性感染的机制尚不清楚。我们研究发现 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。在在这个提议中，我们将测试以下假设：B 细胞抗原呈递会扭曲 CD4+ T 细胞反应布鲁氏菌病会损害疫苗功效并导致慢性感染。本提案的目标#1 我们将研究 B 细胞抗原呈递影响感染控制和调节的机制 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，我们确定如何 B 细胞和 CD4+ T 细胞之间的滤泡相互作用影响抗体产生和 CD4+ 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了解并确定可以的免疫调节策略纳入布鲁氏菌病疫苗的合理设计