Transient TLR Activation Restores Inflammatory Response and Ability To Control Pulmonary Bacterial Infection in Germfree Mice
Transient TLR Activation Restores Inflammatory Response and Ability To Control Pulmonary Bacterial Infection in Germfree Mice
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DOI：
10.4049/jimmunol.1101682
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发表时间：
2012-02-01
影响因子：
4.4
通讯作者：
Souza, Danielle G.
中科院分区：
文献类型：
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作者：
Fagundes, Caio T.;Amaral, Flavio A.;Souza, Danielle G.
哺乳动物暴露在环境表面的共生微生物数量是天文数字。这些共生物种建立了一个复杂的群落，帮助它们的宿主进行一些生理活动。我们已经表明，肠道微生物群的缺乏伴随着活跃的il -10介导的炎症低反应性状态。本研究调查了无菌状态及其低反应表型是否会改变宿主对感染性细菌侵害的抵抗力。在感染肺炎克雷伯菌的无菌小鼠中进行的实验表明，这些动物以il -10依赖的方式对细菌感染非常敏感。在无菌小鼠中，IL-10抑制促炎介质的产生和中性粒细胞的募集，促进病原体的生长和传播。无菌小鼠对LPS有抗性。然而，用几种TLR激动剂刺激这些动物恢复了它们对无菌损伤的炎症反应性。LPS预处理还使无菌小鼠对肺部肺炎克雷伯菌感染产生抗性，消除IL-10的产生，恢复感染无菌小鼠肺部tnf - α和CXCL1的产生和中性粒细胞的动员。这种有效的炎症反应由lps处理的无菌小鼠引起，导致细菌清除和感染后的存活率提高。因此，本地微生物群的宿主定植改变了宿主对环境感染刺激的反应方式，可能是通过激活tlr依赖途径。共生肠道定植能够对宿主的有害伤害做出适当的炎症反应，并增加整个哺乳动物-微生物群财团对环境压力的恢复能力。免疫学杂志，2012,18(8):1411-1420。
Mammals are colonized by an astronomical number of commensal microorganisms on their environmental exposed surfaces. These symbiotic species build up a complex community that aids their hosts in several physiological activities. We have shown that lack of intestinal microbiota is accompanied by a state of active IL-10-mediated inflammatory hyporesponsiveness. The present study investigated whether the germfree state and its hyporesponsive phenotype alter host resistance to an infectious bacterial insult. Experiments performed in germfree mice infected with Klebsiella pneumoniae showed that these animals are drastically susceptible to bacterial infection in an IL-10-dependent manner. In germfree mice, IL-10 restrains proinflammatory mediator production and neutrophil recruitment and favors pathogen growth and dissemination. Germfree mice were resistant to LPS treatment. However, priming of these animals with several TLR agonists recovered their inflammatory responsiveness to sterile injury. LPS pretreatment also rendered germfree mice resistant to pulmonary K. pneumoniae infection, abrogated IL-10 production, and restored TNF-alpha and CXCL1 production and neutrophil mobilization into lungs of infected germfree mice. This effective inflammatory response mounted by LPS-treated germfree mice resulted in bacterial clearance and enhanced survival upon infection. Therefore, host colonization by indigenous microbiota alters the way the host reacts to environmental infectious stimuli, probably through activation of TLR-dependent pathways. Symbiotic gut colonization enables proper inflammatory response to harmful insults to the host, and increases resilience of the entire mammal-microbiota consortium to environmental pressures. The Journal of Immunology, 2012, 188: 1411-1420.