A unifying hypothesis on the central role of reactive oxygen species in bacterial pathogenesis and host defense in C. elegans. (February 2021)

• Record Type: Journal Article
• Authors: Goswamy, Debanjan; Irazoqui, Javier E
• Is Part Of: Current opinion in immunology. Volume 68(2021)
• Page Start: 9
• Page End: 20
• Publication Date: 2021-02
• Subjects: Immunology -- Periodicals; Allergy -- Periodicals; Immunology -- Abstracts -- Periodicals; Allergy -- Abstracts -- Periodicals; 616.079
• DOI: 10.1016/j.coi.2020.08.002
• Languages: English
• ISSNs: 0952-7915

Abstract

Graphical abstract: Highlights: Reactive oxygen species (ROS) are produced through various sources, including mitochondria and DUOX, at sites of infection. ROS function directly as antimicrobials or indirectly as signals to induce host defense. Excess ROS damage organelles, such as the mitochondria and endoplasmic reticulum, and oxidize host biomolecules. Consequences of excess ROS include ATP depletion, disruption of metabolism, and loss of proteostasis. Cytoprotective pathways mitigate ROS-induced damage and counteract organismal failure and death. Abstract : During intestinal infection, microbes induce ROS by various mechanisms in C. elegans. ROS can have beneficial roles, acting as antimicrobials and as signaling molecules that activate cytoprotective pathways. Failure to maintain appropriate levels of ROS causes oxidative stress and cellular damage. This review uses the Damage Response Framework to interpret several recent observations on the relationships between infection, host response, and host damage, with a focus on mechanisms mediated by ROS. We propose a unifying hypothesis that ROS drive a collapse in proteostasis in infected C. elegans, which results in death during unresolved infection. Because the signaling pathways highlighted here are conserved in mammals, the mentioned and future studies can provide new tools of hypothesis generation in human health and disease.