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两种小鼠模型中对脓肿分枝杆菌感染及其抗原免疫反应的比较分析

Comparative analysis of immune responses to Mycobacterium abscessus infection and its antigens in two murine models.

作者信息

Jeon Bo-Young, Kwak Jeongyeon, Lee Seung-Sub, Cho Sangnae, Won Chul Jae, Kim Jin Man, Shin Sung Jae

机构信息

Department of Microbiology and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

出版信息

J Microbiol. 2009 Oct;47(5):633-40. doi: 10.1007/s12275-009-0139-1. Epub 2009 Oct 24.

Abstract

Mycobacterium abscessus has been identified as an emerging pulmonary pathogen in humans. Because little is known regarding immune responses elicited by M. abscessus or its antigens, immunological responses were studied in two murine models subjected to intravenous (high-dose or systemic infection) or pulmonary (low-dose or local infection) inoculation with M. abscessus ATCC 19977. An overall comparison between the two models showed similar patterns of bacterial survival and host immune responses. The colonization of M. abscessus was the highest at 5 days post-infection (dpi) and its elimination was positively correlated with cell-mediated immunity in both challenges. However, an inverse relationship was observed between progressive inflammation and mycobacterial colonization levels in mice infected with a high dose at 14 dpi. Regarding antigens, culture filtrate (CF) of M. abscessus strongly induced IFN-gamma secretion, whereas cellular extract (CE) antigen elicited strong antibody responses. The antibody response to M. abscessus antigens in mice subjected to low-dose infection increased when the cellular immune response decreased over 14 dpi. However, the antibody response for the high-dose infection increased promptly after the infection. In comparison of cytokine expression in lung homogenates after M. abscessus infection, Thl and Th2 cytokines increased simultaneously in the high-dose infection, whereas only cell-mediated immunity developed in the low-dose pulmonary infection. These findings not only enhance our understanding of the immune response to M. abscessus infection according to systemic or pulmonary infection, but may also aid in immunological diagnosis and vaccine development. M. abscessus, murine infection model, immune response, antigens, cytokines.

摘要

脓肿分枝杆菌已被确认为一种新出现的人类肺部病原体。由于对脓肿分枝杆菌或其抗原引发的免疫反应了解甚少,因此在两种小鼠模型中研究了免疫反应,这两种模型分别通过静脉注射(高剂量或全身感染)或肺部接种(低剂量或局部感染)脓肿分枝杆菌ATCC 19977。两种模型之间的总体比较显示出相似的细菌存活模式和宿主免疫反应。脓肿分枝杆菌的定植在感染后5天(dpi)时最高,在两种攻击模型中其清除与细胞介导的免疫呈正相关。然而,在14 dpi时,高剂量感染的小鼠中,进行性炎症与分枝杆菌定植水平之间观察到负相关关系。关于抗原,脓肿分枝杆菌的培养滤液(CF)强烈诱导IFN-γ分泌,而细胞提取物(CE)抗原引发强烈的抗体反应。在14 dpi期间,当细胞免疫反应降低时,低剂量感染小鼠对脓肿分枝杆菌抗原的抗体反应增加。然而,高剂量感染后的抗体反应在感染后迅速增加。比较脓肿分枝杆菌感染后肺匀浆中的细胞因子表达,高剂量感染中Th1和Th2细胞因子同时增加,而低剂量肺部感染中仅发展出细胞介导的免疫。这些发现不仅增进了我们对根据全身或肺部感染对脓肿分枝杆菌感染的免疫反应的理解,而且可能有助于免疫诊断和疫苗开发。脓肿分枝杆菌、小鼠感染模型、免疫反应、抗原、细胞因子。

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