The Natural Cytotoxicity Receptor 1 Contribution to Early Clearance of Streptococcus pneumoniae and to Natural Killer-Macrophage Cross Talk
The Natural Cytotoxicity Receptor 1 Contribution to Early Clearance of Streptococcus pneumoniae and to Natural Killer-Macrophage Cross Talk
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DOI：
10.1371/journal.pone.0023472
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发表时间：
2011-08-22
期刊：
影响因子：
3.7
通讯作者：
Porgador, Angel
中科院分区：
文献类型：
--
作者：
Elhaik-Goldman, Shirin;Kafka, Daniel;Porgador, Angel
自然杀伤（NK）细胞是对抗肿瘤、病毒和细菌感染的关键第一道防线。我们研究了一种主要的活化性自然杀伤细胞受体，天然细胞毒性受体1（NCR 1），在先天性免疫反应中的参与。肺炎感染。我们的研究结果表明，NCR 1受体的存在是必不可少的早期清除S。肺炎。我们在体内研究表明，在S.肺炎感染。NCR 1不介导S的直接识别。肺炎。因此，我们研究了肺巨噬细胞和树突状细胞（DC）作为NK表达的NCR 1参与S.肺炎。在体外，野生型BM衍生的巨噬细胞和DC表达NCR 1配体，并与S.与表达NCR 1的NK细胞相比，用NCR 1缺陷型NK细胞感染的巨噬细胞/DC导致显著更低的IFN γ水平。在体内，肺巨噬细胞和DC的消融不利于S.肺炎。与NCR 1缺陷小鼠相比，NCR 1表达小鼠具有更有效的肺泡巨噬细胞。该结果与NCR 1表达小鼠中NCR 1配体（高）肺巨噬细胞的较高分数相关，与NCR 1配体（迟钝）巨噬细胞相比，其具有更好的吞噬活性。总之，我们的研究结果表明NK表达的NCR 1在S. pneumoniae感染以及NCR 1介导的NK和S.肺炎感染的-巨噬细胞和-DC。
Natural killer (NK) cells serve as a crucial first line of defense against tumors, viral and bacterial infections. We studied the involvement of a principal activating natural killer cell receptor, natural cytotoxicity receptor 1 (NCR1), in the innate immune response to S. pneumoniae infection. Our results demonstrate that the presence of the NCR1 receptor is imperative for the early clearance of S. pneumoniae. We tied the ends in vivo by showing that deficiency in NCR1 resulted in reduced lung NK cell activation and lung IFN gamma production at the early stages of S. pneumoniae infection. NCR1 did not mediate direct recognition of S. pneumoniae. Therefore, we studied the involvement of lung macrophages and dendritic cells (DC) as the mediators of NK-expressed NCR1 involvement in response to S. pneumoniae. In vitro, wild type BM-derived macrophages and DC expressed ligands to NCR1 and co-incubation of S. pneumoniae-infected macrophages/DC with NCR1-deficient NK cells resulted in significantly lesser IFN gamma levels compared to NCR1-expressing NK cells. In vivo, ablation of lung macrophages and DC was detrimental to the early clearance of S. pneumoniae. NCR1-expressing mice had more potent alveolar macrophages as compared to NCR1-deficient mice. This result correlated with the higher fraction of NCR1-ligand(high) lung macrophages, in NCR1-expressing mice, that had better phagocytic activity compared to NCR1-ligand(dull) macrophages. Overall, our results point to the essential contribution of NK-expressed NCR1 in early response to S. pneumoniae infection and to NCR1-mediated interaction of NK and S. pneumoniae infected-macrophages and -DC.