Hommes Tijmen J, van Lieshout Miriam H, van 't Veer Cornelis, Florquin Sandrine, Bootsma Hester J, Hermans Peter W, de Vos Alex F, van der Poll Tom
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
PLoS One. 2015 Dec 16;10(12):e0145138. doi: 10.1371/journal.pone.0145138. eCollection 2015.
Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD) 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/-) and wild-type (Wt) alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39), an isogenic capsule locus deletion mutant (D39Δcps) or serotype 3 S. pneumoniae (6303) via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.
肺炎链球菌是社区获得性肺炎最常见的致病病原体。含核苷酸结合寡聚化结构域（NOD）2是一种位于髓样细胞胞质溶胶中的模式识别受体，能够检测肺炎链球菌的肽聚糖片段。我们在此旨在研究NOD2在肺炎球菌肺炎期间宿主反应中的作用。在体外对NOD2缺陷型（Nod2-/-）和野生型（Wt）肺泡巨噬细胞及中性粒细胞中肺炎链球菌的吞噬作用进行了研究。在随后的体内实验中，通过气道给Nod2-/-和Wt小鼠接种2型肺炎链球菌（D39）、同基因荚膜位点缺失突变体（D39Δcps）或3型肺炎链球菌（6303），并评估细菌的生长、扩散及肺部炎症反应。Nod2-/-肺泡巨噬细胞和血液中性粒细胞在体外对肺炎球菌的内化能力降低。在由肺炎链球菌D39引起的肺炎期间，Nod2-/-小鼠在肺部和远处器官的细菌载量、肺部病理学及中性粒细胞募集方面与Wt小鼠并无差异。虽然Nod2-/-和Wt小鼠在感染毒性更强的肺炎链球菌6303菌株后细菌载量也相似，但Nod2-/-小鼠对通常无毒的无荚膜D39Δcps菌株的细菌清除能力降低。这些结果表明，NOD2在肺炎球菌肺炎期间对宿主防御无作用，且肺炎球菌荚膜会损害NOD2对肺炎链球菌的识别。
