Stenger S, Niazi K R, Modlin R L
Department of Microbiology and Immunology, University of California, Los Angeles, School of Medicine 90095, USA.
J Immunol. 1998 Oct 1;161(7):3582-8.
Intracellular pathogens have developed efficient evasion strategies to survive the defenses of the host immune system. In this study, we describe a new escape mechanism utilized by Mycobacterium tuberculosis that involves the down-regulation of the Ag-presenting molecule CD1 from the cell surface of CD1+ APCs. The loss of CD1 from the cell surface is associated with a complete inhibition of the ability of the infected cells to present Ag to CD1-restricted T cells. The down-regulation of Ag-presenting molecules on CD1+ APC by infection with M. tuberculosis is unique for CD1, since the expression of the classical Ag-presenting molecules MHC class I and MHC class II is not influenced. Our data show that efficient down-regulation of CD1 requires infection of the cells with live mycobacteria, since heat killing of the bacteria completely abrogates the effect. The observed down-regulation is not due to the secretion of cytokines or other host- or pathogen-derived factors. Investigation of upstream events responsible for the down-regulation of CD1 revealed that infection with live M. tuberculosis decreased the steady state CD1-mRNA levels. This study introduces a novel evasion mechanism of M. tuberculosis that could contribute to persistence of intracellular infection by avoiding immune recognition.
细胞内病原体已形成有效的逃避策略，以在宿主免疫系统的防御中存活。在本研究中，我们描述了结核分枝杆菌利用的一种新的逃逸机制，该机制涉及从CD1 +抗原呈递细胞（APC）的细胞表面下调抗原呈递分子CD1。细胞表面CD1的缺失与受感染细胞向CD1限制性T细胞呈递抗原的能力完全抑制相关。结核分枝杆菌感染导致CD1 + APC上抗原呈递分子的下调对CD1而言是独特的，因为经典抗原呈递分子MHC I类和MHC II类的表达不受影响。我们的数据表明，CD1的有效下调需要活分枝杆菌感染细胞，因为细菌的热灭活完全消除了这种效应。观察到的下调不是由于细胞因子或其他宿主或病原体衍生因子的分泌。对负责CD1下调的上游事件的研究表明，活结核分枝杆菌感染降低了稳态CD1 - mRNA水平。本研究介绍了结核分枝杆菌的一种新的逃逸机制，该机制可能通过避免免疫识别而有助于细胞内感染的持续存在。
