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Granulocytes impose...
Granulocytes impose a tight bottleneck upon the gut luminal pathogen population during Salmonella typhimurium colitis.
- Article/chapterEnglish2014
Publisher, publication year, extent ...
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2014-12-18
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Public Library of Science (PLoS),2014
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-309865
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-309865URI
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https://doi.org/10.1371/journal.ppat.1004557DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Topological, chemical and immunological barriers are thought to limit infection by enteropathogenic bacteria. However, in many cases these barriers and their consequences for the infection process remain incompletely understood. Here, we employed a mouse model for Salmonella colitis and a mixed inoculum approach to identify barriers limiting the gut luminal pathogen population. Mice were infected via the oral route with wild type S. Typhimurium (S. Tm) and/or mixtures of phenotypically identical but differentially tagged S. Tm strains ("WITS", wild-type isogenic tagged strains), which can be individually tracked by quantitative real-time PCR. WITS dilution experiments identified a substantial loss in tag/genetic diversity within the gut luminal S. Tm population by days 2-4 post infection. The diversity-loss was not attributable to overgrowth by S. Tm mutants, but required inflammation, Gr-1+ cells (mainly neutrophilic granulocytes) and most likely NADPH-oxidase-mediated defense, but not iNOS. Mathematical modelling indicated that inflammation inflicts a bottleneck transiently restricting the gut luminal S. Tm population to approximately 6000 cells and plating experiments verified a transient, inflammation- and Gr-1+ cell-dependent dip in the gut luminal S. Tm population at day 2 post infection. We conclude that granulocytes, an important clinical hallmark of S. Tm-induced inflammation, impose a drastic bottleneck upon the pathogen population. This extends the current view of inflammation-fuelled gut-luminal Salmonella growth by establishing the host response in the intestinal lumen as a double-edged sword, fostering and diminishing colonization in a dynamic equilibrium. Our work identifies a potent immune defense against gut infection and reveals a potential Achilles' heel of the infection process which might be targeted for therapy.
Added entries (persons, corporate bodies, meetings, titles ...)
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Diard, Médéric
(author)
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Sellin, Mikael E
(author)
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Chouffane, Elsa-Sarah
(author)
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Trautwein-Weidner, Kerstin
(author)
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Periaswamy, Balamurugan
(author)
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Slack, Emma
(author)
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Dolowschiak, Tamas
(author)
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Stecher, Bärbel
(author)
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Loverdo, Claude
(author)
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Regoes, Roland R
(author)
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Hardt, Wolf-Dietrich
(author)
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In:PLoS Pathogens: Public Library of Science (PLoS)10:121553-73661553-7374
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Maier, Lisa
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Diard, Médéric
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Sellin, Mikael E
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Chouffane, Elsa- ...
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Trautwein-Weidne ...
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Periaswamy, Bala ...
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Slack, Emma
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Dolowschiak, Tam ...
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Stecher, Bärbel
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Loverdo, Claude
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Regoes, Roland R
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PLoS Pathogens
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Uppsala University