Transcription of Inflammatory Genes in the Lung after Infection with Community-Associated Methicillin-Resistant Staphylococcus aureus: a Role for Panton-Valentine Leukocidin?
Transcription of Inflammatory Genes in the Lung after Infection with Community-Associated Methicillin-Resistant Staphylococcus aureus: a Role for Panton-Valentine Leukocidin?
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DOI：
10.1128/iai.00021-09
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发表时间：
2009-05-01
影响因子：
3.1
通讯作者：
Daum, Robert S.
中科院分区：
文献类型：
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作者：
Montgomery, Christopher P.;Daum, Robert S.
由社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）分离株引起的坏死性肺炎越来越常见，而且往往很严重。CA-MRSA感染后肺部的早期炎症反应在很大程度上仍不明确。此外，许多工作者假设Panton-Valentine杀白细胞素（PVL）是CA-MRSA坏死性肺炎的关键毒力决定因素。我们假设用USA 300 CA-MRSA分离株对大鼠进行气管内接种将导致参与免疫应答的基因的早期表达，并且这将与坏死性肺炎的炎症和组织破坏特征相关。此外，我们假设感染PVL缺失突变体将导致减弱的早期宿主反应。用USA 300（菌株LAC）亚致死接种物感染大鼠，导致研究的大多数细胞因子、趋化因子和炎症受体基因转录物的表达迅速增加，如定量实时逆转录酶PCR（qRT-PCR）所评估。增加的基因转录随后是炎症，增加肺部细菌存活和坏死性肺炎。用菌株LAC感染和用菌株LAC Delta pvl（lukSF-PV缺失突变体）感染导致不可区分的疾病，如通过死亡率、体内细菌回收率和肺病理学评估的。通过qRT-PCR对炎性基因转录的评估也揭示了在用LAC感染后和在用LAC Delta pvl感染后，在死亡的动物中或在存活至接种后24小时的动物中几乎没有差异。我们的结论是，在坏死性肺炎的大鼠模型中，有一个早期的，活跃的炎症转录反应与中性粒细胞的招聘和组织破坏。lukSF-PV的缺失没有改变肺中对CA-MRSA的早期免疫应答。
Necrotizing pneumonia caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates is increasingly common and frequently severe. The early inflammatory response in the lung after CA-MRSA infection remains largely undefined. Additionally, many workers have hypothesized that the Panton-Valentine leukocidin (PVL) is a key virulence determinant in CA-MRSA necrotizing pneumonia. We hypothesized that intratracheal inoculation of rats with a USA300 CA-MRSA isolate would result in early expression of genes involved in the immune response and that this would correlate with inflammation and tissue destruction characteristic of necrotizing pneumonia. In addition, we hypothesized that infection with a PVL deletion mutant would result in an attenuated early host response. Infection of rats with a sublethal inoculum of USA300 (strain LAC) resulted in rapid increased expression of most cytokine, chemokine, and inflammatory receptor gene transcripts studied, as assessed by quantitative real-time reverse transcriptase PCR (qRT-PCR). The increased gene transcription was followed by inflammation, increased bacterial survival in the lungs, and necrotizing pneumonia. Infection with strain LAC and infection with strain LAC Delta pvl (lukSF-PV deletion mutant) resulted in indistinguishable diseases, as assessed by mortality, in vivo bacterial recovery, and pulmonary pathology. Assessment of the transcription of inflammatory genes by qRT-PCR also revealed little difference after infection with LAC and after infection with LAC Delta pvl, either in animals that died or in animals that survived to 24 h after inoculation. We conclude that in a rat model of necrotizing pneumonia, there was an early, brisk inflammatory transcriptional response associated with neutrophil recruitment and tissue destruction. Deletion of lukSF-PV did not alter the early immune response to CA-MRSA in the lung.