Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia
Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia
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DOI：
10.1128/iai.00037-15
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发表时间：
2015-10-01
影响因子：
3.1
通讯作者：
Pier, Gerald B.
中科院分区：
文献类型：
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作者：
Gauguet, Stefanie;D'Ortona, Samantha;Pier, Gerald B.
肠道微生物群的组成，特别是节段性丝状细菌(SFB)的存在，调节着胃肠道的免疫功能，但肠道微生物群在肺宿主防御中的作用还没有得到很好的研究。我们测试了通过获取SFB改变肠道微生物区系是否通过诱导17型免疫来影响金黄色葡萄球菌肺炎的易感性。在急性肺部感染模型中，用耐甲氧西林金黄色葡萄球菌攻击肠道定植不同的C57BL/6小鼠。比较了来自不同供应商的小鼠、来自两个供应商的小鼠共住后、感染前口服SFB的小鼠以及有和没有外源性IL-22或抗IL-22抗体的小鼠的细菌负荷、支气管肺泡灌洗液(BALF)细胞数量、细胞类型和细胞因子水平。缺乏SFB的小鼠比有SFB的小鼠发生更严重的金黄色葡萄球菌肺炎，这表明肺部的细菌负荷、肺部炎症和死亡率更高。当SFB阴性小鼠通过与SFB阳性小鼠共居或口服SFB时，在其肠道微生物区系中获得SFB时，这种差异被缩小。肺泡灌洗液中IL-22水平升高，BALF中IL-22(+)TCRβ(+)细胞和中性粒细胞数量增多，SFB阳性小鼠肺组织中17型免疫效应物水平较高，而SFB阴性小鼠肺组织中17型免疫效应物水平较高。外源性IL-22对金黄色葡萄球菌肺炎的保护作用。小鼠肠道微生物区系，特别是SFB的存在，促进了肺17型免疫和对金黄色葡萄球菌肺炎的抵抗力，而IL-22对严重的肺部葡萄球菌感染具有保护作用。
Th17 immunity in the gastrointestinal tract is regulated by the intestinal microbiota composition, particularly the presence of segmented filamentous bacteria (sfb), but the role of the intestinal microbiota in pulmonary host defense is not well explored. We tested whether altering the gut microbiota by acquiring sfb influences the susceptibility to staphylococcal pneumonia via induction of type 17 immunity. Groups of C57BL/6 mice which differed in their intestinal colonization with sfb were challenged with methicillin-resistant Staphylococcus aureus in an acute lung infection model. Bacterial burdens, bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels were compared between mice from different vendors, mice from both vendors after cohousing, mice given sfb orally prior to infection, and mice with and without exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb developed more severe S. aureus pneumonia than mice colonized with sfb, as indicated by higher bacterial burdens in the lungs, lung inflammation, and mortality. This difference was reduced when sfb-negative mice acquired sfb in their gut microbiota through cohousing with sfb-positive mice or when given sfb orally. Levels of type 17 immune effectors in the lung were higher after infection in sfb-positive mice and increased in sfb-negative mice after acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers of IL-22(+) TCR beta(+) cells and neutrophils in BALF. Exogenous IL-22 protected mice from S. aureus pneumonia. The murine gut microbiota, particularly the presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection.