Laboratory of Cancer ImmunoMetabolism, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
J Cell Sci. 2021 Mar 8;134(5):jcs252148. doi: 10.1242/jcs.252148.
Host-derived antimicrobial peptides play an important role in the defense against extracellular bacterial infections. However, the capacity of antimicrobial peptides derived from macrophages as potential antibacterial effectors against intracellular pathogens remains unknown. In this study, we report that normal (wild-type, WT) mouse macrophages increased their expression of cathelin-related antimicrobial peptide (CRAMP, encoded by ) after infection by viable or stimulation with inactivated and its product lipopolysaccharide (LPS), a process involving activation of NF-κB followed by protease-dependent conversion of CRAMP from an inactive precursor to an active form. The active CRAMP was required by WT macrophages for elimination of phagocytosed , with participation of autophagy-related proteins ATG5, LC3-II and LAMP-1, as well as for aggregation of the bacteria with p62 (also known as SQSTM1). This process was impaired in macrophages, resulting in retention of intracellular bacteria and fragmentation of macrophages. These results indicate that CRAMP is a critical component in autophagy-mediated clearance of intracellular by mouse macrophages.
宿主来源的抗菌肽在抵御细胞外细菌感染中发挥着重要作用。然而，巨噬细胞来源的抗菌肽作为潜在的抗细胞内病原体的抗菌效应物的能力尚不清楚。在这项研究中，我们报告称，正常（野生型，WT）小鼠巨噬细胞在感染活的 或用失活的 及其产物脂多糖（LPS）刺激后，会增加其 cathelin 相关抗菌肽（CRAMP，由 编码）的表达，这一过程涉及 NF-κB 的激活，随后是蛋白酶依赖性的将 CRAMP 从无活性的前体转化为有活性的形式。WT 巨噬细胞需要活性 CRAMP 来清除吞噬的 ，这需要自噬相关蛋白 ATG5、LC3-II 和 LAMP-1 的参与，以及与 p62（也称为 SQSTM1）的细菌聚集。在 巨噬细胞中，这个过程受损，导致细胞内细菌的保留和巨噬细胞的碎片化。这些结果表明，CRAMP 是小鼠巨噬细胞通过自噬清除细胞内 的关键组成部分。
