Tian Xianbin, Liu Yanni, Zhu Kun, An Haoran, Feng Jie, Zhang Linqi, Zhang Jing-Ren
School of Basic Medical Sciences, Center for Infection Biology, Tsinghua University , Beijing, China.
Tsinghua-Peking Center for Life Sciences, Tsinghua University , Beijing, China.
J Exp Med. 2025 Feb 3;222(2). doi: 10.1084/jem.20240735. Epub 2024 Dec 24.
The interception of blood-borne bacteria in the liver defines the outcomes of invasive bacterial infections, but the mechanisms of this antibacterial immunity are not fully understood. This study shows that natural antibodies (nAbs) to capsules enable liver macrophage Kupffer cells (KCs) to rapidly capture and kill blood-borne encapsulated bacteria in mice. Affinity pulldown with serotype-10A capsular polysaccharides (CPS10A) of Streptococcus pneumoniae (Spn10A) led to the identification of CPS10A-binding nAbs in serum. The CPS10A-antibody interaction enabled KCs to capture Spn10A bacteria from the bloodstream, in part through complement receptors on KCs. The nAbs were found to recognize the β1-6-linked galactose branch of CPS10A and similar moieties of serotype-39 S. pneumoniae and serotype-K50 Klebsiella pneumoniae capsules. More importantly, the nAbs empowered KCs to capture serotype-39 S. pneumoniae and serotype-K50 K. pneumoniae in the liver. Collectively, our data have revealed a highly effective immune function of nAb against encapsulated bacteria and emphasize the concept of treating septic encapsulated bacterial diseases with monoclonal antibodies.
肝脏对血源细菌的拦截决定了侵袭性细菌感染的结局，但这种抗菌免疫的机制尚未完全明确。本研究表明，针对荚膜的天然抗体（nAbs）可使肝脏巨噬细胞库普弗细胞（KCs）快速捕获并杀死小鼠体内的血源荚膜细菌。用肺炎链球菌10A血清型（Spn10A）的10A血清型荚膜多糖（CPS10A）进行亲和拉下实验，鉴定出血清中与CPS10A结合的nAbs。CPS10A与抗体的相互作用使KCs能够从血流中捕获Spn10A细菌，部分是通过KCs上的补体受体。研究发现，这些nAbs可识别CPS10A的β1-6连接半乳糖分支以及39血清型肺炎链球菌和K50血清型肺炎克雷伯菌荚膜的类似部分。更重要的是，这些nAbs使KCs能够在肝脏中捕获39血清型肺炎链球菌和K50血清型肺炎克雷伯菌。总体而言，我们的数据揭示了nAb针对荚膜细菌的高效免疫功能，并强调了用单克隆抗体治疗败血性荚膜细菌疾病的概念。
