Uncoupling of invasive bacterial mucosal immunogenicity from pathogenicity

Simona P. Pfister, Olivier P. Schären, Luca Beldi, Andrea Printz, Matheus D. Notter, Mohana Mukherjee, Hai Li, Julien P. Limenitakis, Joel P. Werren, Disha Tandon, Miguelangel Cuenca, Stefanie Hagemann, Stephanie S. Uster, Miguel A. Terrazos, Mercedes Gomez de Agüero, Christian M. Schürch, Fernanda M. Coelho, Roy Curtiss, Emma Slack, Maria L. Balmer and Siegfried Hapfelmeier ()
Additional contact information
Simona P. Pfister: University of Bern
Olivier P. Schären: University of Bern
Luca Beldi: University of Bern
Andrea Printz: University of Bern
Matheus D. Notter: University of Bern
Mohana Mukherjee: University of Bern
Hai Li: Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM) Inselspital
Julien P. Limenitakis: Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM) Inselspital
Joel P. Werren: University of Bern
Disha Tandon: University of Bern
Miguelangel Cuenca: University of Bern
Stefanie Hagemann: University of Bern
Stephanie S. Uster: University of Bern
Miguel A. Terrazos: University of Bern
Mercedes Gomez de Agüero: Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM) Inselspital
Christian M. Schürch: University of Bern
Fernanda M. Coelho: University of Bern
Roy Curtiss: Arizona State University
Emma Slack: D-HEST
Maria L. Balmer: University of Basel
Siegfried Hapfelmeier: University of Bern

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15891-9

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