In vivo regulation of replicative Legionella pneumophila lung infection by endogenous interleukin-12
In vivo regulation of replicative Legionella pneumophila lung infection by endogenous interleukin-12
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DOI：
10.1128/iai.66.1.65-69.1998
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发表时间：
1998-01-01
影响因子：
3.1
通讯作者：
Fantone, JC
中科院分区：
文献类型：
--
作者：
Brieland, JK;Remick, DG;Fantone, JC
采用复制性嗜肺军团菌（L. pneumophila）小鼠模型，研究了内源性白细胞介素12（IL-12）在调节肺内军团菌生长中的体内作用。嗜肺性肺部感染。用10（6）L.嗜肺细胞/小鼠）导致IL-12的诱导，这先于细菌从肺中清除。通过给予IL-12中和抗血清抑制内源性IL-12活性，导致感染后5天内细菌肺内生长增强（与未处理的L.嗜肺菌感染的小鼠）。因为IL-12先前已显示调节细胞因子的表达，包括γ干扰素（IFN-γ）、肿瘤坏死因子α（TNF-α）和IL-10，其调节L.嗜肺细胞生长，内源性IL-12对这些细胞因子在复制L.随后评估了嗜肺菌肺部感染。这些实验的结果表明，TNF-α活性显著降低，而IFN-γ和IL-10在肺中的蛋白水平相似，在L.与类似感染的未处理小鼠相比，给予IL-12抗血清的嗜肺细胞感染小鼠。总之，这些结果表明IL-12对于复制型L.并提示肺内生长调节L.内源性IL-12介导的嗜肺细胞凋亡至少部分由TNF-α介导。
The in vivo role of endogenous interleukin 12 (IL-12) in modulating intrapulmonary growth of Legionella pneumophila was assessed by using a murine model of replicative L. pneumophila lung infection. Intratracheal inoculation of A/J mice with virulent bacteria (10(6) L. pneumophila cells per mouse) resulted in induction of IL-12, which preceded clearance of the bacteria from the lung. Inhibition of endogenous IL-12 activity, via administration of IL-12 neutralizing antiserum, resulted in enhanced intrapulmonary growth of the bacteria within 5 days postinfection (compared to untreated L. pneumophila-infected mice). Because IL-12 has previously been shown to modulate the expression of cytokines, including gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-10, which regulate L. pneumophila growth, immunomodulatory effects of endogenous IL-12 on intrapulmonary levels of these cytokines during replicative L. pneumophila lung infection were subsequently assessed. Results of these experiments demonstrated that TNF-alpha activity was significantly lower, while protein levels of IFN-gamma and IL-10 in the lung were similar, in L. pneumophila-infected mice administered IL-12 antiserum, compared to similarly infected untreated mice. Together, these results demonstrate that IL-12 is critical for resolution of replicative L. pneumophila lung infection and suggest that regulation of intrapulmonary growth of L. pneumophila by endogenous IL-12 is mediated, at least in part, by TNF-alpha.