Hwang Insu, Mori Kenichiro, Ohtani Katsuki, Matsuda Yasuyuki, Roy Nitai, Kim YounUck, Suzuki Yasuhiko, Wakamiya Nobutaka
Department of Microbiology and Immunochemistry, Asahikawa Medical University, Asahikawa, Japan.
J Innate Immun. 2017;9(2):217-228. doi: 10.1159/000453316. Epub 2017 Jan 10.
Collectins are C-type lectins that are involved in innate immunity as pattern recognition molecules. Recently, collectin kidney 1 (CL-K1) has been discovered, and in vitro studies have shown that CL-K1 binds to microbes and activates the lectin complement pathway. However, in vivo functions of CL-K1 against microbes have not been elucidated. To investigate the biological functions of CL-K1, we generated CL-K1 knockout (CL-K1-/-) mice and then performed a Streptococcus pneumoniae infection analysis. First, we found that recombinant human CL-K1 bound to S. pneumoniae in a calcium-dependent manner, and induced complement activation. CL-K1-/- mice sera formed less C3 deposition on S. pneumoniae. Furthermore, immunofluorescence analysis in the wild-type (WT) mice demonstrated that CL-K1 and C3 were localized on S. pneumoniae in infected lungs. CL-K1-/- mice revealed decreased phagocytosis of S. pneumoniae. Consequently, less S. pneumoniae clearance was observed in their lungs. CL-K1-/- mice showed severe pulmonary inflammation and weight loss in comparison with WT mice. Finally, the decreased clearance and severe pulmonary inflammation caused by S. pneumoniae infection might cause higher CL-K1-/- mice lethality. Our results suggest that CL-K1 might play an important role in host protection against S. pneumoniae infection through the activation of the lectin complement pathway.
凝集素是一类C型凝集素，作为模式识别分子参与固有免疫。最近，凝集素肾1（CL-K1）被发现，体外研究表明CL-K1可结合微生物并激活凝集素补体途径。然而，CL-K1在体内针对微生物的功能尚未阐明。为了研究CL-K1的生物学功能，我们构建了CL-K1基因敲除（CL-K1-/-）小鼠，然后进行了肺炎链球菌感染分析。首先，我们发现重组人CL-K1以钙依赖方式结合肺炎链球菌，并诱导补体激活。CL-K1-/-小鼠血清在肺炎链球菌上形成的C3沉积较少。此外，野生型（WT）小鼠的免疫荧光分析表明，CL-K1和C3定位于感染肺组织中的肺炎链球菌上。CL-K1-/-小鼠显示肺炎链球菌的吞噬作用降低。因此，在它们的肺部观察到肺炎链球菌清除减少。与WT小鼠相比，CL-K1-/-小鼠表现出严重的肺部炎症和体重减轻。最后，肺炎链球菌感染导致的清除减少和严重肺部炎症可能导致CL-K1-/-小鼠更高的致死率。我们的结果表明，CL-K1可能通过激活凝集素补体途径在宿主抵御肺炎链球菌感染中发挥重要作用。
