Marshall N E, Ziegler H K
Department of Microbiology and Immunology, Emory University School of Medicine, Rollins Research Center, Atlanta, GA 30322.
J Immunol. 1991 Oct 1;147(7):2333-9.
We previously have found that the endotoxin (LPS) of Gram-negative bacteria is a major determinant of macrophage Ia induction during infection with these organisms. Specifically, i.p. injection of Gram-negative bacteria elicits a striking macrophage Ia response in LPS-responder mice but virtually no response in LPS-low-responder mice. As an extension of these findings, in this report we have tested the hypothesis that the inability of LPS-low responder mice to mount an Ia response during Gram-negative infection may in turn impair their capacity for generation of appropriate antibacterial T cell responses. Our results demonstrate that for a variety Gram-negative organisms (Salmonella typhimurium, Salmonella minnesota, and Escherichia coli), both macrophage Ia induction and the generation of Ag-specific T cell responses are controlled by the lps gene. We also have asked whether the expression of additional toxins (other than LPS) by infecting Gram-negative organisms can "override" this lps gene control of macrophage and T cell responses. We have found that infection of LPS-low-responder mice with an E. coli strain that expresses a hemolytic exotoxin (Hly) leads to the induction of macrophage Ia expression as well as the generation of T cell responses to both the Hly molecule and to other E. coli-associated Ag, whereas no responses are generated during infection with a Hly- strain. This result suggests that LPS-low responder mice have no inherent defect in T cell responsiveness to Gram-negative bacterial Ag but rather that these mice fail to receive an LPS-mediated signal required for the induction of Ia expression and subsequent generation of peritoneal T cell immunity. These findings, when taken together with results presented in the accompanying paper, strengthen the argument that bacterial toxin production (and the ability of the host to respond to the toxin) can represent a critical determinant of the induction of macrophage Ia expression and in turn, of Ag-specific T cell responses during bacterial infection.
我们先前发现，革兰氏阴性菌的内毒素（LPS）是这些细菌感染期间巨噬细胞Ia诱导的主要决定因素。具体而言，腹腔注射革兰氏阴性菌会在LPS反应性小鼠中引发显著的巨噬细胞Ia反应，但在LPS低反应性小鼠中几乎没有反应。作为这些发现的延伸，在本报告中，我们测试了以下假设：LPS低反应性小鼠在革兰氏阴性菌感染期间无法产生Ia反应，这反过来可能会损害它们产生适当抗菌T细胞反应的能力。我们的结果表明，对于多种革兰氏阴性菌（鼠伤寒沙门氏菌、明尼苏达沙门氏菌和大肠杆菌），巨噬细胞Ia诱导和抗原特异性T细胞反应的产生均受lps基因控制。我们还询问了感染革兰氏阴性菌时表达的其他毒素（除LPS外）是否能“超越”这种对巨噬细胞和T细胞反应的lps基因控制。我们发现，用表达溶血外毒素（Hly）的大肠杆菌菌株感染LPS低反应性小鼠，会导致巨噬细胞Ia表达的诱导以及对Hly分子和其他大肠杆菌相关抗原的T细胞反应的产生，而感染Hly-菌株时则不会产生反应。这一结果表明，LPS低反应性小鼠在对革兰氏阴性菌抗原的T细胞反应性方面没有内在缺陷，而是这些小鼠未能接收到诱导Ia表达和随后产生腹膜T细胞免疫所需的LPS介导信号。这些发现与随附论文中呈现的结果一起，强化了这样一种观点，即细菌毒素产生（以及宿主对毒素的反应能力）可能是细菌感染期间巨噬细胞Ia表达诱导以及进而抗原特异性T细胞反应的关键决定因素。
