Genotoxin-producing Salmonella enterica induces tissue-specific types of DNA damage and DNA damage response outcomesShow others and affiliations
2023 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1270449
Article in journal (Refereed) Published
Abstract [en]
Introduction: Typhoid toxin-expressing Salmonella enterica causes DNA damage in the intestinal mucosa in vivo, activating the DNA damage response (DDR) in the absence of inflammation. To understand whether the tissue microenvironment constrains the infection outcome, we compared the immune response and DDR patterns in the colon and liver of mice infected with a genotoxigenic strain or its isogenic control strain.
Methods: In situ spatial transcriptomic and immunofluorescence have been used to assess DNA damage makers, activation of the DDR, innate immunity markers in a multiparametric analysis.
Result: The presence of the typhoid toxin protected from colonic bacteria-induced inflammation, despite nuclear localization of p53, enhanced co-expression of type-I interferons (IfnbI) and the inflammasome sensor Aim2, both classic features of DNA-break-induced DDR activation. These effects were not observed in the livers of either infected group. Instead, in this tissue, the inflammatory response and DDR were associated with high oxidative stress-induced DNA damage.
Conclusions: Our work highlights the relevance of the tissue microenvironment in enabling the typhoid toxin to suppress the host inflammatory response in vivo.
Place, publisher, year, edition, pages
Frontiers Media S.A., 2023. Vol. 14, article id 1270449
Keywords [en]
bacterial genotoxin, DNA damage response, inflammasome, inflammation, tissue specificity
National Category
Immunology Microbiology
Identifiers
URN: urn:nbn:se:umu:diva-220315DOI: 10.3389/fimmu.2023.1270449ISI: 001150445700001PubMedID: 38274797Scopus ID: 2-s2.0-85183041210OAI: oai:DiVA.org:umu-220315DiVA, id: diva2:1837330
Funder
Swedish Cancer Society, 20 0699 PjFSwedish Research Council, 2021-00960The Kempe Foundations, SMK-1962The Kempe Foundations, JCK-1826The Kempe Foundations, JCK-3110Cancerforskningsfonden i Norrland, AMP20-993Cancerforskningsfonden i Norrland, AMP 17-8842024-02-132024-02-132024-02-13Bibliographically approved