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Chronic obstructive pulmonary disease and asthma-associated Proteobacteria but not commensal Prevotella spp. promote Toll-like receptor 2-independent lung inflammation and pathology

机译:慢性阻塞性肺疾病和与哮喘有关的变形杆菌而非共通的普罗沃氏菌属会促进Toll样受体2独立性肺部炎症和病理

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摘要

Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system.
机译:对健康人类呼吸道的最新研究表明,含有革兰氏阴性普氏杆菌属的共生细菌菌群可以定殖。然而,这些细菌在呼吸系统中的免疫学特性仍然未知。在这里,我们比较了对三种革兰氏阴性共生普雷沃特氏菌菌株(黑色素氮丙酸杆菌,南半球杆菌和唾液酸杆菌)和三种革兰氏阴性致病性变形杆菌的先天性呼吸道免疫应答,已知这三种细菌可定殖于慢性阻塞性肺疾病(COPD)和哮喘患者的肺部(流感嗜血杆菌B,不可分型的流感嗜血杆菌和卡他莫拉菌)。普列沃氏菌属。发现和致病性变形杆菌在鼠肺细胞上具有先天炎症能力的内在差异。在小鼠体内,不可分型的流感嗜血杆菌引起严重的Toll样受体2(TLR2)独立的COPD样炎症,其特征是主要的气道嗜中性粒细胞增多,肺组织中嗜中性细胞因子/趋化因子谱的表达以及肺免疫病理学。相比之下,南芥(P.nanceiensis)诱导的嗜中性气道炎症减少,并且没有可检测到的肺部病理。有趣的是,革兰氏阴性菌南希毕赤酵母的气道反应完全是TLR2依赖性的。这些发现证明了革兰氏阴性气道共杆菌Prevotella spp的较弱的发炎特性。可能会使这些细菌在呼吸系统免疫系统中得以耐受。

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