Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity.
Citrobacter rodentium infection is a mouse model for the important human diarrheal infection caused by enteropathogenic E. coli (EPEC). The pathogenesis of both species is very similar and depends on their unique ability to form intimately epithelium-adherent microcolonies, also known as "attac...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1006476 |
| _version_ | 1818734940731211776 |
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| author | Stefanie Buschor Miguelangel Cuenca Stephanie S Uster Olivier P Schären Maria L Balmer Miguel A Terrazos Christian M Schürch Siegfried Hapfelmeier |
| author_facet | Stefanie Buschor Miguelangel Cuenca Stephanie S Uster Olivier P Schären Maria L Balmer Miguel A Terrazos Christian M Schürch Siegfried Hapfelmeier |
| author_sort | Stefanie Buschor |
| collection | DOAJ |
| description | Citrobacter rodentium infection is a mouse model for the important human diarrheal infection caused by enteropathogenic E. coli (EPEC). The pathogenesis of both species is very similar and depends on their unique ability to form intimately epithelium-adherent microcolonies, also known as "attachment/effacement" (A/E) lesions. These microcolonies must be dynamic and able to self-renew by continuous re-infection of the rapidly regenerating epithelium. It is unknown whether sustained epithelial A/E lesion pathogenesis is achieved through re-infection by planktonic bacteria from the luminal compartment or local spread of sessile bacteria without a planktonic phase. Focusing on the earliest events as C. rodentium becomes established, we show here that all colonic epithelial A/E microcolonies are clonal bacterial populations, and thus depend on local clonal growth to persist. In wild-type mice, microcolonies are established exclusively within the first 18 hours of infection. These early events shape the ongoing intestinal geography and severity of infection despite the continuous presence of phenotypically virulent luminal bacteria. Mechanistically, induced resistance to A/E lesion de-novo formation is mediated by TLR-MyD88/Trif-dependent signaling and is induced specifically by virulent C. rodentium in a virulence gene-dependent manner. Our data demonstrate that the establishment phase of C. rodentium pathogenesis in vivo is restricted to a very short window of opportunity that determines both disease geography and severity. |
| first_indexed | 2024-12-18T00:13:21Z |
| format | Article |
| id | doaj.art-7f1a6c77af7244ae9b99a84bbeb9e58d |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-18T00:13:21Z |
| publishDate | 2017-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-7f1a6c77af7244ae9b99a84bbeb9e58d2022-12-21T21:27:36ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-06-01136e100647610.1371/journal.ppat.1006476Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity.Stefanie BuschorMiguelangel CuencaStephanie S UsterOlivier P SchärenMaria L BalmerMiguel A TerrazosChristian M SchürchSiegfried HapfelmeierCitrobacter rodentium infection is a mouse model for the important human diarrheal infection caused by enteropathogenic E. coli (EPEC). The pathogenesis of both species is very similar and depends on their unique ability to form intimately epithelium-adherent microcolonies, also known as "attachment/effacement" (A/E) lesions. These microcolonies must be dynamic and able to self-renew by continuous re-infection of the rapidly regenerating epithelium. It is unknown whether sustained epithelial A/E lesion pathogenesis is achieved through re-infection by planktonic bacteria from the luminal compartment or local spread of sessile bacteria without a planktonic phase. Focusing on the earliest events as C. rodentium becomes established, we show here that all colonic epithelial A/E microcolonies are clonal bacterial populations, and thus depend on local clonal growth to persist. In wild-type mice, microcolonies are established exclusively within the first 18 hours of infection. These early events shape the ongoing intestinal geography and severity of infection despite the continuous presence of phenotypically virulent luminal bacteria. Mechanistically, induced resistance to A/E lesion de-novo formation is mediated by TLR-MyD88/Trif-dependent signaling and is induced specifically by virulent C. rodentium in a virulence gene-dependent manner. Our data demonstrate that the establishment phase of C. rodentium pathogenesis in vivo is restricted to a very short window of opportunity that determines both disease geography and severity.https://doi.org/10.1371/journal.ppat.1006476 |
| spellingShingle | Stefanie Buschor Miguelangel Cuenca Stephanie S Uster Olivier P Schären Maria L Balmer Miguel A Terrazos Christian M Schürch Siegfried Hapfelmeier Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity. PLoS Pathogens |
| title | Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity. |
| title_full | Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity. |
| title_fullStr | Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity. |
| title_full_unstemmed | Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity. |
| title_short | Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity. |
| title_sort | innate immunity restricts citrobacter rodentium a e pathogenesis initiation to an early window of opportunity |
| url | https://doi.org/10.1371/journal.ppat.1006476 |
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