Liu Guanghui, Gradstedt Henrik, Ermert David, Englund Emelie, Singh Birendra, Su Yu-Ching, Johansson Martin E, Aspberg Anders, Agarwal Vaibhav, Riesbeck Kristian, Blom Anna M
Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden;
Division of Clinical Microbiology, Department of Translational Medicine, Lund University, SE-205 02 Malmö, Sweden;
J Immunol. 2016 Feb 1;196(3):1249-58. doi: 10.4049/jimmunol.1502071. Epub 2015 Dec 28.
Moraxella catarrhalis is a respiratory tract pathogen commonly causing otitis media in children and acute exacerbations in patients suffering from chronic obstructive pulmonary disease. Cartilage oligomeric matrix protein (COMP) functions as a structural component in cartilage, as well as a regulator of complement activity. Importantly, COMP is detected in resident macrophages and monocytes, alveolar fluid, and the endothelium of blood vessels in lung tissue. We show that the majority of clinical isolates of M. catarrhalis (n = 49), but not other tested bacterial pathogens, bind large amounts of COMP. COMP interacts directly with the ubiquitous surface protein A2 of M. catarrhalis. Binding of COMP correlates with survival of M. catarrhalis in human serum by inhibiting bactericidal activity of the complement membrane attack complex. Moreover, COMP inhibits phagocytic killing of M. catarrhalis by human neutrophils. We further observed that COMP reduces bacterial adhesion and uptake by human lung epithelial cells, thus protecting M. catarrhalis from intracellular killing by epithelial cells. Taken together, our findings uncover a novel mechanism that M. catarrhalis uses to evade host innate immunity.
卡他莫拉菌是一种呼吸道病原体，通常可导致儿童中耳炎以及慢性阻塞性肺疾病患者的急性加重。软骨寡聚基质蛋白（COMP）在软骨中作为一种结构成分发挥作用，同时也是补体活性的调节剂。重要的是，在驻留巨噬细胞和单核细胞、肺泡液以及肺组织血管内皮中可检测到COMP。我们发现，大多数卡他莫拉菌临床分离株（n = 49），而非其他检测的细菌病原体，能结合大量COMP。COMP直接与卡他莫拉菌普遍存在的表面蛋白A2相互作用。COMP的结合通过抑制补体膜攻击复合物的杀菌活性，与卡他莫拉菌在人血清中的存活相关。此外，COMP抑制人中性粒细胞对卡他莫拉菌的吞噬杀伤。我们进一步观察到，COMP减少人肺上皮细胞对细菌的黏附和摄取，从而保护卡他莫拉菌免受上皮细胞的胞内杀伤。综上所述，我们的研究结果揭示了卡他莫拉菌用于逃避宿主固有免疫的一种新机制。
