Nonhematopoietic Cells Control the Outcome of Infection with Listeria monocytogenes in a Nucleotide Oligomerization Domain 1-Dependent Manner
Nonhematopoietic Cells Control the Outcome of Infection with Listeria monocytogenes in a Nucleotide Oligomerization Domain 1-Dependent Manner
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DOI：
10.1128/iai.01068-08
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发表时间：
2009-07-01
影响因子：
3.1
通讯作者：
Rottenberg, Martin E.
中科院分区：
文献类型：
--
作者：
Mosa, Ahmed;Trumstedt, Christian;Rottenberg, Martin E.
我们分析了单核细胞增生李斯特菌感染过程中胞质先天识别受体核苷酸寡聚化结构域1（NOD 1）的防御作用。NOD 1缺失的小鼠对高剂量或低剂量的L.单核细胞增多症，如通过细菌载量和存活率测量的。NOD 1也控制L.单核细胞增多症NOD 1（-/-）小鼠对再感染的易感性增加与Escherichia特异性T细胞的触发受损无关，并且观察到类似水平的共刺激分子或树突状细胞的活化。感染WT小鼠的腹膜中F480（+）Gr 1（+）炎性单核细胞数量高于感染NOD 1（-/-）小鼠的腹膜，而F480（+）Gr 1（+）中性粒细胞数量低于感染NOD 1（-/-）小鼠的腹膜。我们确定，非造血细胞占NOD 1介导的耐药性L。骨髓辐射嵌合体中的单核细胞增多症。感染L.单核细胞增生或用不同的Toll样受体配体刺激。与WT对照相比，NOD 1（-/-）BMM、星形胶质细胞和成纤维细胞均显示单核细胞增生李斯特菌的细胞内生长增强。γ-干扰素介导的一氧化氮产生和对L。NOD 1（-/-）BMM抑制单核细胞增生。因此，NOD 1赋予非造血细胞介导的抗感染L。单核细胞增多症和控制细胞内细菌生长在不同的细胞群体在体外。
We analyzed the defensive role of the cytosolic innate recognition receptor nucleotide oligomerization domain 1 (NOD1) during infection with Listeria monocytogenes. Mice lacking NOD1 showed increased susceptibility to systemic intraperitoneal and intravenous infection with high or low doses of L. monocytogenes, as measured by the bacterial load and survival. NOD1 also controlled dissemination of L. monocytogenes into the brain. The increased susceptibility to reinfection of NOD1(-/-) mice was not associated with impaired triggering of listeria-specific T cells, and similar levels of costimulatory molecules or activation of dendritic cells was observed. Higher numbers of F480(+) Gr1(+) inflammatory monocytes and lower numbers of F480(+) Gr1(+) neutrophils were recruited into the peritoneum of infected WT mice than into the peritoneum of infected NOD1(-/-) mice. We determined that nonhematopoietic cells accounted for NOD1-mediated resistance to L. monocytogenes in bone marrow radiation chimeras. The levels of NOD1 mRNA in fibroblasts and bone marrow-derived macrophages (BMM) were upregulated after infection with L. monocytogenes or stimulation with different Toll-like receptor ligands. NOD1(-/-) BMM, astrocytes, and fibroblasts all showed enhanced intracellular growth of L monocytogenes compared to WT controls. Gamma interferon-mediated nitric oxide production and inhibition of L. monocytogenes growth were hampered in NOD1(-/-) BMM. Thus, NOD1 confers nonhematopoietic cell-mediated resistance to infection with L. monocytogenes and controls intracellular bacterial growth in different cell populations in vitro.