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Updated: Nov 9, 2025

High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
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Influence of the microenvironment on modulation of the host response by typhoid toxin

Océane C B Martin1, Anna Bergonzini2, Maria Lopez Chiloeches2

  • 1Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Cell Reports
|April 7, 2021
PubMed

Insights

Bacterial genotoxins from Salmonella infection unexpectedly protect against intestinal inflammation by inducing DNA damage and senescence, creating an anti-inflammatory environment. This protective effect is lost during active colitis, highlighting context-dependent host-microbial interactions.

Area of Science:

  • Microbiology
  • Immunology
  • Genetics

Background:

  • Bacterial genotoxins induce DNA damage response (DDR) in vitro.
  • Genotoxins are produced by Gram-negative bacteria prevalent in inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients.
  • The role of genotoxins during infection is poorly understood.

Purpose of the Study:

  • To investigate the role of typhoid toxin in host-microbial interactions during health and disease.
  • To elucidate the in vivo effects of genotoxigenic Salmonella infection on host immunity.

Main Methods:

  • Infection of mice with genotoxigenic Salmonella.
  • Assessment of DNA fragmentation, senescence, and inflammatory markers in vivo.
  • Comparison of infection outcomes in healthy mice versus mice with acute colitis.

Main Results:

  • Genotoxigenic Salmonella infection protected mice from intestinal inflammation.
  • Active genotoxins induced DNA fragmentation and senescence in vivo, uncoupled from inflammation.
  • An anti-inflammatory environment was unexpectedly induced by genotoxin presence.
  • This anti-inflammatory response was abrogated in mice with acute colitis.

Conclusions:

  • Bacterial genotoxin-induced DDR has a complex, context-dependent role in modulating host immune responses.
  • Genotoxins can unexpectedly induce anti-inflammatory effects, challenging previous assumptions.
  • The interplay between bacterial genotoxins, DDR, and the immune system is critical in health and disease states like IBD and CRC.
Keywords:
Ataxia-telangiectasia mutated (ATM)bacterial genotoxinscolitisimmune responseimmunomodulationmicroenviromentsenescencetyphoid toxin

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