Host-directed therapy for bacterial infections -Modulation of the phagolysosome pathway-

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...

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Main Authors: Toshihiko Taya, Fumiya Teruyama, Satoshi Gojo
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1227467/full
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author Toshihiko Taya
Fumiya Teruyama
Fumiya Teruyama
Satoshi Gojo
author_facet Toshihiko Taya
Fumiya Teruyama
Fumiya Teruyama
Satoshi Gojo
author_sort Toshihiko Taya
collection DOAJ
description 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.
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spelling doaj.art-42f89f4ea8d04089888aeec95883f5f32023-09-30T22:04:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12274671227467Host-directed therapy for bacterial infections -Modulation of the phagolysosome pathway-Toshihiko Taya0Fumiya Teruyama1Fumiya Teruyama2Satoshi Gojo3Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto, JapanPharmacology Research Department, Tokyo New Drug Research Laboratories, Kowa Company, Ltd., Tokyo, JapanDepartment of Regenerative Medicine, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto, JapanDepartment of Regenerative Medicine, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto, JapanBacterial 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1227467/fullbacterial infectionimmune evasionhost-directed therapysepsisantimicrobial resistancephagocytosis
spellingShingle Toshihiko Taya
Fumiya Teruyama
Fumiya Teruyama
Satoshi Gojo
Host-directed therapy for bacterial infections -Modulation of the phagolysosome pathway-
Frontiers in Immunology
bacterial infection
immune evasion
host-directed therapy
sepsis
antimicrobial resistance
phagocytosis
title Host-directed therapy for bacterial infections -Modulation of the phagolysosome pathway-
title_full Host-directed therapy for bacterial infections -Modulation of the phagolysosome pathway-
title_fullStr Host-directed therapy for bacterial infections -Modulation of the phagolysosome pathway-
title_full_unstemmed Host-directed therapy for bacterial infections -Modulation of the phagolysosome pathway-
title_short Host-directed therapy for bacterial infections -Modulation of the phagolysosome pathway-
title_sort host directed therapy for bacterial infections modulation of the phagolysosome pathway
topic bacterial infection
immune evasion
host-directed therapy
sepsis
antimicrobial resistance
phagocytosis
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1227467/full
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