Uncoupling of invasive bacterial mucosal immunogenicity from pathogenicity.
Adaptor Proteins, Vesicular Transport
/ metabolism
Animals
Antigens, Bacterial
Caspase 1
/ metabolism
Caspases, Initiator
/ metabolism
Cell Proliferation
Gastrointestinal Microbiome
Immunity, Innate
Immunity, Mucosal
Immunoglobulin A
/ immunology
Inflammation
Intestinal Mucosa
/ microbiology
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Myeloid Differentiation Factor 88
/ metabolism
Nod1 Signaling Adaptor Protein
/ metabolism
Nod2 Signaling Adaptor Protein
/ metabolism
Salmonella Infections
/ microbiology
Salmonella typhimurium
/ pathogenicity
Signal Transduction
Virulence
Virulence Factors
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
03
07
2019
accepted:
30
03
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
4
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32332737
doi: 10.1038/s41467-020-15891-9
pii: 10.1038/s41467-020-15891-9
pmc: PMC7181798
doi:
Substances chimiques
Adaptor Proteins, Vesicular Transport
0
Antigens, Bacterial
0
Immunoglobulin A
0
Myd88 protein, mouse
0
Myeloid Differentiation Factor 88
0
Nod1 Signaling Adaptor Protein
0
Nod1 protein, mouse
0
Nod2 Signaling Adaptor Protein
0
Nod2 protein, mouse
0
TICAM-1 protein, mouse
0
Virulence Factors
0
Casp4 protein, mouse
EC 3.4.22.-
Caspases, Initiator
EC 3.4.22.-
Casp1 protein, mouse
EC 3.4.22.36
Caspase 1
EC 3.4.22.36
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1978Subventions
Organisme : NIAID NIH HHS
ID : R01 AI056289
Pays : United States
Commentaires et corrections
Type : ErratumIn
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