Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Pharmacology Research Department, Tokyo New Drug Research Laboratories, Kowa Company, Ltd., Tokyo, Japan.
Front Immunol. 2023 Sep 29;14:1227467. doi: 10.3389/fimmu.2023.1227467. eCollection 2023.
Bacterial infections still impose a significant burden on humanity, even though antimicrobial agents have long since been developed. In addition to individual severe infections, the f fatality rate of sepsis remains high, and the threat of antimicrobial-resistant bacteria grows with time, putting us at inferiority. Although tremendous resources have been devoted to the development of antimicrobial agents, we have yet to recover from the lost ground we have been driven into. Looking back at the evolution of treatment for cancer, which, like infectious diseases, has the similarity that host immunity eliminates the lesion, the development of drugs to eliminate the tumor itself has shifted from a single-minded focus on drug development to the establishment of a treatment strategy in which the de-suppression of host immunity is another pillar of treatment. In infectious diseases, on the other hand, the development of therapies that strengthen and support the immune system has only just begun. Among innate immunity, the first line of defense that bacteria encounter after invading the host, the molecular mechanisms of the phagolysosome pathway, which begins with phagocytosis to fusion with lysosome, have been elucidated in detail. Bacteria have a large number of strategies to escape and survive the pathway. Although the full picture is still unfathomable, the molecular mechanisms have been elucidated for some of them, providing sufficient clues for intervention. In this article, we review the host defense mechanisms and bacterial evasion mechanisms and discuss the possibility of host-directed therapy for bacterial infection by intervening in the phagolysosome pathway.
细菌感染仍然给人类带来巨大负担，尽管抗菌药物早已问世。除了个别严重感染外，脓毒症的病死率仍然很高，而且随着时间的推移，对抗菌药物耐药的细菌的威胁也在增加，使我们处于劣势。尽管我们投入了大量资源来开发抗菌药物，但我们仍未能从被迫陷入的困境中恢复过来。回顾癌症治疗的发展历程，它与传染病有相似之处，即宿主免疫消除病变，消除肿瘤本身的药物开发已经从单纯的药物开发转向建立治疗策略，其中抑制宿主免疫是治疗的另一个支柱。另一方面，在传染病中，增强和支持免疫系统的治疗方法的发展才刚刚开始。在先天免疫中，细菌侵入宿主后遇到的第一道防线是吞噬体途径的分子机制，该途径从吞噬作用开始，最终与溶酶体融合，其详细机制已经阐明。细菌有许多逃避和存活的策略。尽管全貌仍难以捉摸，但其中一些的分子机制已经阐明，为干预提供了充分的线索。本文综述了宿主防御机制和细菌逃避机制，并讨论了通过干预吞噬体途径对细菌感染进行宿主定向治疗的可能性。
