Τίτλος:
Influence of the microenvironment on modulation of the host response by typhoid toxin
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Bacterial genotoxins cause DNA damage in eukaryotic cells, resulting in activation of the DNA damage response (DDR) in vitro. These toxins are produced by Gram-negative bacteria, enriched in the microbiota of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. However, their role in infection remains poorly characterized. We address the role of typhoid toxin in modulation of the host-microbial interaction in health and disease. Infection with a genotoxigenic Salmonella protects mice from intestinal inflammation. We show that the presence of an active genotoxin promotes DNA fragmentation and senescence in vivo, which is uncoupled from an inflammatory response and unexpectedly associated with induction of an anti-inflammatory environment. The anti-inflammatory response is lost when infection occurs in mice with acute colitis. These data highlight a complex context-dependent crosstalk between bacterial-genotoxin-induced DDR and the host immune response, underlining an unexpected role for bacterial genotoxins. © 2021 The Author(s)
Συγγραφείς:
Martin, O.C.B.
Bergonzini, A.
Lopez Chiloeches, M.
Paparouna, E.
Butter, D.
Theodorou, S.D.P.
Haykal, M.M.
Boutet-Robinet, E.
Tebaldi, T.
Wakeham, A.
Rhen, M.
Gorgoulis, V.G.
Mak, T.
Pateras, I.S.
Frisan, T.
Λέξεις-κλειδιά:
toxin; ATM protein; Atm protein, mouse; mutagenic agent; toxin, animal experiment; animal model; animal tissue; Article; colitis; controlled study; DNA fragmentation; enteritis; female; immune response; in vivo study; inflammation; male; microbial interaction; microenvironment; mouse; nonhuman; priority journal; Salmonella; senescence; animal; C57BL mouse; drug effect; host pathogen interaction; immunity; immunology; metabolism; microbiology; pathology; physiology; tumor microenvironment; typhoid fever, Animals; Ataxia Telangiectasia Mutated Proteins; Cellular Microenvironment; Colitis; Host-Pathogen Interactions; Immunity; Inflammation; Mice, Inbred C57BL; Mutagens; Salmonella; Toxins, Biological; Typhoid Fever
DOI:
10.1016/j.celrep.2021.108931
