Immunopathology of early and subclinical Mycobacterium avium subspecies paratuberculosis infection in calves

犊牛早期和亚临床鸟分枝杆菌亚种副结核感染的免疫病理学

• 批准号: 418348-2012
• 负责人: Plattner, Brandon
• 金额: $ 2.26万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=551357
• 关键词: Immunopathology; early; subclinical; Mycobacterium; avium

This research is designed to enhance our understanding of host innate immunity and resistance to mycobacterial infection. I am interested in how interactions between host innate immune cells and invading mycobacteria influence the outcome of infection. Mycobacterium avium subspecies paratuberculosis (Map) causes Johne's disease, an important and costly intestinal disease affecting beef and dairy cattle in Canada and around the world. Global efforts to control mycobacterial infections including Map have achieved limited success and this is largely because the fundamental mechanisms leading to success (elimination of infection) or failure (establishment of persistent infection) of host immunity are unknown. Gamma-delta T lymphocytes are a unique class of innate immune cells that have been recently implicated as orchestrators of host defense by directing adaptive immunity which is known to be essential for clearance of invading mycobacteria. We have observed recruitment of gamma-delta T cells to Map infection sites in calves, but a mechanistic understanding of their function in host immunity has not been elucidated. In these studies, we will investigate how these innate cells direct host immunity during initial Map infection: 1) how they are recruited to early infection sites and 2) how they affect function of other immune cells (macrophages, dendritic cells) which are vital for success of host immunity. We will also examine gamma-delta T cells within the intestine of calves with subclinical intestinal Map infection, and how they direct either maintenance of persistent infection (latency) or progression to clinical disease. The results will lead to improved strategies to reduce mycobacterial infections and identify subclinically-infected individuals as well as enhanced recognition of the role of innate immune cells in controlling bacterial infections.

本研究旨在提高我们对宿主先天免疫和抵抗分枝杆菌感染的认识。 我感兴趣的是宿主先天免疫细胞和入侵分枝杆菌之间的相互作用如何影响感染的结果。 鸟分枝杆菌副结核亚种（MAP）导致约翰氏病，这是一种影响加拿大和世界各地肉牛和奶牛的重要且昂贵的肠道疾病。 全球控制分枝杆菌感染的努力（包括Map）取得了有限的成功，这主要是因为导致宿主免疫成功（消除感染）或失败（建立持续感染）的基本机制尚不清楚。 γ-δ T淋巴细胞是一类独特的先天性免疫细胞，其最近被认为是通过指导适应性免疫来协调宿主防御的，已知适应性免疫对于清除入侵的分枝杆菌是必不可少的。 我们已经观察到γ-δ T细胞的招募，以映射感染部位的小牛，但其在宿主免疫功能的机制的理解还没有得到阐明。 在这些研究中，我们将研究这些先天性细胞在初始Map感染期间如何指导宿主免疫：1）它们如何被招募到早期感染部位，以及2）它们如何影响其他免疫细胞（巨噬细胞，树突状细胞）的功能，这些免疫细胞对宿主免疫的成功至关重要。 我们还将检查患有亚临床肠道Map感染的小牛肠道内的γ-δ T细胞，以及它们如何指导持续感染（潜伏期）的维持或临床疾病的进展。 这些结果将导致改进的策略，以减少分枝杆菌感染和识别亚临床感染的个体，以及增强对先天免疫细胞在控制细菌感染中的作用的认识。