Murine macrophages differentially produce proinflammatory cytokines after infection with virulent vs. avirulent Legionella pneumophila
Murine macrophages differentially produce proinflammatory cytokines after infection with virulent vs. avirulent Legionella pneumophila
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DOI：
10.1002/jlb.67.6.863
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发表时间：
2000-06-01
影响因子：
5.5
通讯作者：
Friedman, H
中科院分区：
文献类型：
--
作者：
McHugh, SL;Yamamoto, Y;Friedman, H
在遗传允许的A/J小鼠面前，嗜肺军团菌在巯基乙酸盐诱导的腹腔巨噬细胞中很容易复制，但无毒力的L。嗜肺菌则不然。巨噬细胞感染L.已经研究了嗜肺菌，但是细菌毒力与巨噬细胞的免疫应答（例如促炎细胞因子产生）的相关性还没有很好地理解。在这方面，在体外用毒性与无毒力嗜肺军团菌感染的巨噬细胞培养物中检测细胞因子肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1 α、IL-1 β和IL-6的产生，用毒性军团菌感染来自A/J小鼠的巨噬细胞。pneumophila上调这些细胞因子的mRNA表达，而无毒力细菌仅导致细胞因子mRNA的轻微或不可检测的增加。嗜肺菌诱导巨噬细胞产生相对高水平的TNF-α、IL-1 α、IL-1 β和IL-6蛋白，如通过酶联免疫吸附测定所测量的，而无毒力细菌仅诱导低或通常不可检测量的这些细胞因子。因此，这些结果表明，来自易感A/J小鼠的鼠巨噬细胞在体外容易感染有毒性的嗜肺军团菌，并被刺激产生促炎急性期细胞因子TNF-α、IL-1 α、IL-1 β和IL-6，但无毒性的嗜肺军团菌。嗜肺菌则没有。巨噬细胞对强毒与无毒的嗜肺军团菌感染诱导这些促炎细胞因子的这种差异可能是这些细胞内细菌诱导的发病机制中的重要因素。
Virulent Legionella pneumophila replicate readily in thioglycollate-elicited peritoneal macrophages front genetically permissive A/J mice, but avirulent L. pneumophila do not. The production of cytokines by macrophages infected with L. pneumophila has been studied, but the correlation of bacterial virulence with immune responses of macrophages, such as proinflammatory cytokine production, is not well understood. In this regard, production of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1 alpha, IL-1 beta, and IL-6 were examined in macrophage cultures infected in vitro with virulent vs. avirulent L, pneumophila, infection of macrophages from A/J mice with the virulent L. pneumophila up-regulated mRNA expression for these cytokines, whereas avirulent bacteria resulted in only a slight or no detectable increase in cytokine mRNA, Similarly, virulent L. pneumophila induced the macrophages to produce relatively high levels of TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6 proteins as measured by enzyme-linked immunosorbent assays, whereas avirulent bacteria induced only low or often undetectable amounts of these cytokines. Thus, these results show the murine macrophages from susceptible A/J mice are readily infected with virulent L, pneumophila in vitro and stimulated to produce the proinflammatory acute-phase cytokines TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6, but avirulent L. pneumophila did not. Such differences in induction of these proinflammatory cytokines by macrophages in response to virulent vs. avirulent L, pneumophila infections may be an important factor in the pathogenesis induced by these intracellular bacteria.