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PreprintCited by 4Escherichia coli research studiesImmune Response and InflammationImmune responses and vaccinations

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Cooperation between physiological defenses and immune resistance produces asymptomatic carriage of a lethal bacterial pathogen

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Chen, Grischa Y., Thorup, Natalia R., Miller, Abigail J., Li, Yao-Cheng, Ayres, Janelle S.·2023·Science Advances
DOI 10.1101/2023.01.22.525099PMC PMC10289649

Preprint — published as 10.1126/sciadv.adg8719

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Abstract

Animals have evolved two defense strategies to survive infections. Antagonistic strategies include mechanisms of immune resistance that operate to sense and kill invading pathogens. Cooperative or physiological defenses mediate host adaptation to the infected state, limiting physiological damage and disease, without killing the pathogen, and have been shown to cause asymptomatic carriage and transmission of lethal pathogens. Here we demonstrate that physiological defenses cooperate with the adaptive immune response to generate long-term asymptomatic carriage of the lethal enteric murine pathogen, Citrobacter rodentium . Asymptomatic carriage of genetically virulent C. rodentium provided immune resistance against subsequent infections. Host immune protection was dependent on systemic antibody responses and pathogen virulence behavior, rather than the recognition of specific virulent factor antigens. Finally, we demonstrate that an avirulent strain of C. rodentium in the field has background mutations in two genes that are important for LPS structure. Our work reveals novel insight into how asymptomatic infections can arise mechanistically with immune resistance, mediating exclusion of phenotypically virulent enteric pathogen to promote asymptomatic carriage.

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Metadata

Authors
Chen, G. Y., Thorup, N. R., Miller, A. J., Li, Y.-C., & Ayres, J. S.
Affiliations
Salk Institute for Biological Studies (US)
Corresponding author
Ayres, Janelle S.
ORCID
Venue
Science Advances
Publisher
openRxiv
Published
2023-01-22
Volume
9
Issue
25
Pages
eadg8719-eadg8719
ISSN
2375-2548 (ISSN-L)
DOI
10.1101/2023.01.22.525099
PMC
PMC10289649
OpenAlex
W4381799163
Cited by
4
References
1
Citations by year
2026: 1 · 2024: 3
FWCI
0.74
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • Larry L. Hillblom Foundation
  • Leona M. and Harry B. Helmsley Charitable Trust
  • University of Texas Southwestern Medical Center
  • University of Melbourne
  • Queensland Government
  • NOMIS Stiftung
  • Australian Research Data Commons
  • National Institutes of Health (P30 014195)
  • Defense Advanced Research Projects Agency (YFA15 D15AP00097)
  • National Cancer Institute (CCSG:P30 014195, P30014195, P30CA014195)
  • National Institute of Allergy and Infectious Diseases (DP1AI144249, R01AI114929)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
asymptomatic carriage, immune resistance, collaborative defense, Citrobacter rodentium, enteric bacterial infection, systemic antibody response, pathogen virulence, avirulent strains, host-pathogen interaction

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