Uncoupling of invasive bacterial mucosal immunogenicity from pathogenicity.

Pfister, Simona; Schären, Olivier P.; Beldi, Luca; Printz, Andrea; Notter, Matheus D.; Mukherjee, Mohana; Li, Hai; Limenitakis, Julien P.; Werren, Joel P.; Tandon, Disha; Cuenca Vera, Miguelangel; Hagemann, Stefanie Claudia; Uster, Stephanie S.; Terrazos, Miguel A.; Gomez de Agüero, Mercedes; Schürch, Christian M.; Matos Coelho, Fernanda; Curtiss, Roy; Slack, Emma; Balmer, Maria L.; ... (2020). Uncoupling of invasive bacterial mucosal immunogenicity from pathogenicity. Nature Communications, 11(1), p. 1978. Springer Nature 10.1038/s41467-020-15891-9

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There is the notion that infection with a virulent intestinal pathogen induces generally stronger mucosal adaptive immunity than the exposure to an avirulent strain. Whether the associated mucosal inflammation is important or redundant for effective induction of immunity is, however, still unclear. Here we use a model of auxotrophic Salmonella infection in germ-free mice to show that live bacterial virulence factor-driven immunogenicity can be uncoupled from inflammatory pathogenicity. Although live auxotrophic Salmonella no longer causes inflammation, its mucosal virulence factors remain the main drivers of protective mucosal immunity; virulence factor-deficient, like killed, bacteria show reduced efficacy. Assessing the involvement of innate pathogen sensing mechanisms, we show MYD88/TRIF, Caspase-1/Caspase-11 inflammasome, and NOD1/NOD2 nodosome signaling to be individually redundant. In colonized animals we show that microbiota metabolite cross-feeding may recover intestinal luminal colonization but not pathogenicity. Consequent immunoglobulin A immunity and microbial niche competition synergistically protect against Salmonella wild-type infection.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Clinical Microbiology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Infection Serology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Pfister, Simona; Schären, Olivier Pascal; Beldi, Luca; Printz, Andrea; Notter Dias, Matheus; Mukherjee, Mohana; Li, Hai; Limenitakis, Julien Periclis Jean; Werren, Joel Pascal; Tandon, Disha; Cuenca Vera, Miguelangel; Hagemann, Stefanie Claudia; Uster, Stephanie Sarah; Terrazos Miani, Miguel Angel; Gomez de Agüero Tamargo, Maria de la Mercedes; Matos Coelho, Fernanda and Hapfelmeier, Siegfried Hektor

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Springer Nature

Language:

English

Submitter:

Andrea Stettler

Date Deposited:

06 Aug 2020 10:44

Last Modified:

19 Nov 2020 11:37

Publisher DOI:

10.1038/s41467-020-15891-9

PubMed ID:

32332737

BORIS DOI:

10.7892/boris.145611

URI:

https://boris.unibe.ch/id/eprint/145611

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