Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136.
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136
J Immunol. 2018 Nov 1;201(9):2710-2720. doi: 10.4049/jimmunol.1800365. Epub 2018 Sep 24.
Perforin-2, the product of the gene, limits the spread and dissemination of bacterial pathogens in vivo. It is highly expressed in murine and human phagocytes, and macrophages lacking Perforin-2 are compromised in their ability to kill phagocytosed bacteria. In this study, we used serovar Typhimurium as a model intracellular pathogen to elucidate the mechanism of Perforin-2's bactericidal activity. In vitro Perforin-2 was found to facilitate the degradation of Ags contained within the envelope of phagocytosed bacteria. In contrast, degradation of a representative surface Ag was found to be independent of Perforin-2. Consistent with our in vitro results, a protease-sensitive, periplasmic superoxide dismutase (SodCII) contributed to the virulence of Typhimurium in Perforin-2 knockout but not wild-type mice. In aggregate, our studies indicate that Perforin-2 breaches the envelope of phagocytosed bacteria, facilitating the delivery of proteases and other antimicrobial effectors to sites within the bacterial cell.
穿孔素-2 是基因的产物，限制了细菌病原体在体内的传播和扩散。它在鼠类和人类吞噬细胞中高度表达，缺乏穿孔素-2 的巨噬细胞在吞噬细菌的杀伤能力上受到损害。在这项研究中，我们使用鼠伤寒沙门氏菌作为一种模型胞内病原体来阐明穿孔素-2 的杀菌活性的机制。体外研究发现，穿孔素-2 有助于降解吞噬细菌包膜内的抗原。相比之下，一种代表性的表面抗原的降解被发现与穿孔素-2 无关。与我们的体外结果一致的是，一种蛋白酶敏感的周质超氧化物歧化酶（SodCII）有助于鼠伤寒沙门氏菌在穿孔素-2 敲除而非野生型小鼠中的毒力。总的来说，我们的研究表明，穿孔素-2 破坏了吞噬细菌的包膜，促进了蛋白酶和其他抗菌效应物递送到细菌细胞内的部位。
