Abdillahi Suado M, Bober Marta, Nordin Sara, Hallgren Oskar, Baumgarten Maria, Erjefält Jonas, Westergren-Thorsson Gunilla, Bjermer Leif, Riesbeck Kristian, Egesten Arne, Mörgelin Matthias
Division of Infection Medicine, Lund University, Lund, Sweden.
J Innate Immun. 2015;7(5):506-17. doi: 10.1159/000381213. Epub 2015 Apr 25.
Moraxella catarrhalis is a Gram-negative human mucosal commensal and pathogen. It is a common cause of exacerbation in chronic obstructive pulmonary disease (COPD). During the process of infection, host colonization correlates with recognition of host molecular patterns. Importantly, in COPD patients with compromised epithelial integrity the underlying extracellular matrix is exposed and provides potential adhesive targets. Collagen VI is a ubiquitous fibrillar component in the airway mucosa and has been attributed both adhesive and killing properties against Gram-positive bacteria. However, less is known regarding Gram-negative microorganisms. Therefore, in the present study, the interaction of M. catarrhalis with collagen VI was characterized. We found that collagen VI is upregulated in the airways of COPD patients and exposed upon epithelial desquamation. Ex vivo, we inoculated airway biopsies and fibroblasts from COPD patients with M. catarrhalis. The bacteria specifically adhered to collagen VI-containing matrix fibrils. In vitro, purified collagen VI microfibrils bound to bacterial surface structures. The primary adhesion target was mapped to the collagen VI α2-chain. Upon exposure to collagen VI, bacteria were killed by membrane destabilization in physiological conditions. These previously unknown properties of collagen VI provide novel insights into the extracellular matrix innate immunity by quickly entrapping and killing pathogen intruders.
卡他莫拉菌是一种革兰氏阴性人类黏膜共生菌和病原体。它是慢性阻塞性肺疾病（COPD）病情加重的常见原因。在感染过程中，宿主定植与宿主分子模式的识别相关。重要的是，在上皮完整性受损的COPD患者中，潜在的细胞外基质会暴露出来，并提供潜在的黏附靶点。Ⅵ型胶原蛋白是气道黏膜中普遍存在的纤维成分，对革兰氏阳性菌具有黏附及杀伤特性。然而，对于革兰氏阴性微生物的了解较少。因此，在本研究中，对卡他莫拉菌与Ⅵ型胶原蛋白的相互作用进行了表征。我们发现，Ⅵ型胶原蛋白在COPD患者的气道中上调，并在上皮脱落后暴露出来。在体外，我们用卡他莫拉菌接种了COPD患者的气道活检组织和成纤维细胞。细菌特异性黏附于含Ⅵ型胶原蛋白的基质纤维。在体外，纯化的Ⅵ型胶原蛋白微纤维与细菌表面结构结合。主要黏附靶点定位于Ⅵ型胶原蛋白α2链。暴露于Ⅵ型胶原蛋白后，细菌在生理条件下因膜不稳定而被杀死。Ⅵ型胶原蛋白这些此前未知的特性为细胞外基质先天免疫通过快速捕获和杀死病原体入侵者提供了新的见解。
