Restriction of Legionella pneumophila growth in macrophages requires the concerted action of cytokine and Naip5/Ipaf signalling pathways
Restriction of Legionella pneumophila growth in macrophages requires the concerted action of cytokine and Naip5/Ipaf signalling pathways
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DOI：
10.1111/j.1462-5822.2007.00963.x
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发表时间：
2007-10-01
影响因子：
3.4
通讯作者：
Dietrich, William F.
中科院分区：
文献类型：
--
作者：
Coers, Joern;Vance, Russell E.;Dietrich, William F.
来自C57 BL/6（B6）小鼠品系的巨噬细胞限制嗜肺军团菌的细胞内生长，而A/J巨噬细胞是高度允许的。B6巨噬细胞限制军团菌生长的机制仍然知之甚少，但已知需要胞质微生物传感器Naip 5（Birc 1 e）和Ipaf。我们假设Naip 5和Ipaf可能与巨噬细胞中的其他抗菌信号通路合作。事实上，我们发现缺乏肿瘤坏死因子（TNF）-α或I型干扰素（IFN）信号的巨噬细胞允许L。即使在功能性Naip 5和Ipaf等位基因的存在下。类似地，缺乏Naip 5和/或Ipaf信号传导的巨噬细胞是允许的，即使我们发现Naip 5或Ipaf对于TNF-α和I型IFN的诱导不是必需的。因此，我们的数据表明，B6巨噬细胞限制L.嗜肺菌比以前认识到的更复杂，并且涉及细胞因子和细胞内微生物传感器信号传导途径的协同作用。
Macrophages from the C57BL/6 (B6) mouse strain restrict intracellular growth of Legionella pneumophila, whereas A/J macrophages are highly permissive. The mechanism by which B6 macrophages restrict Legionella growth remains poorly understood, but is known to require the cytosolic microbe sensors Naip5 (Birc1e) and Ipaf. We hypothesized that Naip5 and Ipaf may act in partnership with other antimicrobial signalling pathways in macrophages. Indeed, we found that macrophages lacking either tumour necrosis factor (TNF)-alpha or type I interferon (IFN) signalling are permissive for growth of L. pneumophila, even in the presence of functional Naip5 and Ipaf alleles. Similarly, macrophages lacking Naip5 and/or Ipaf signalling were permissive even though we found that Naip5 or Ipaf were not required for induction of TNF-alpha and type I IFN. Therefore, our data suggest that the mechanism by which B6 macrophages restrict intracellular replication of L. pneumophila is more complex than previously appreciated, and involves the concerted action of cytokine and intracellular microbe sensor signalling pathways.