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PMID: 18268033 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Microbe sampling by mucosal dendritic cells is a discrete, MyD88-independent step in DeltainvG S. Typhimurium colitis.

The Journal of experimental medicine ·Vol. 205 ·No. 2 ·2008-02-18 ·Pages 437-50

Hapfelmeier S, Müller AJ, Stecher B, Kaiser P, Barthel M, Endt K, Eberhard M, Robbiani R, Jacobi CA, Heikenwalder M, Kirschning C, Jung S, Stallmach T, Kremer M, Hardt WD

Abstract

Intestinal dendritic cells (DCs) are believed to sample and present commensal bacteria to the gut-associated immune system to maintain immune homeostasis. How antigen sampling pathways handle intestinal pathogens remains elusive. We present a murine colitogenic Salmonella infection model that is highly dependent on DCs. Conditional DC depletion experiments revealed that intestinal virulence of S. Typhimurium SL1344 DeltainvG mutant lacking a functional type 3 secretion system-1 (DeltainvG)critically required DCs for invasion across the epithelium. The DC-dependency was limited to the early phase of infection when bacteria colocalized with CD11c(+)CX3CR1(+) mucosal DCs. At later stages, the bacteria became associated with other (CD11c(-)CX3CR1(-)) lamina propria cells, DC depletion no longer attenuated the pathology, and a MyD88-dependent mucosal inflammation was initiated. Using bone marrow chimeric mice, we showed that the MyD88 signaling within hematopoietic cells, which are distinct from DCs, was required and sufficient for induction of the colitis. Moreover, MyD88-deficient DCs supported transepithelial uptake of the bacteria and the induction of MyD88-dependent colitis. These results establish that pathogen sampling by DCs is a discrete, and MyD88-independent, step during the initiation of a mucosal innate immune response to bacterial infection in vivo.

MeSH Terms
Animals CD11 Antigens/immunology CX3C Chemokine Receptor 1 Cecum/immunology,pathology Colitis/immunology,pathology Dendritic Cells/immunology Intestinal Mucosa/immunology Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Myeloid Differentiation Factor 88/deficiency,genetics,immunology Receptors, Chemokine/immunology Salmonella Infections/immunology,pathology Salmonella typhimurium
Chemicals
CD11 Antigens CX3C Chemokine Receptor 1 Cx3cr1 protein, mouse Myd88 protein, mouse Myeloid Differentiation Factor 88 Receptors, Chemokine
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Hapfelmeier Siegfried
Institute of Microbiology, D-BIOL, ETH Zürich, CH-8093 Zürich, Switzerland.
Müller Andreas J
Stecher Bärbel
Kaiser Patrick
Barthel Manja
Endt Kathrin
Eberhard Matthias
Robbiani Riccardo
Jacobi Christoph A
Heikenwalder Mathias
Kirschning Carsten
Jung Steffen
Stallmach Thomas
Kremer Marcus
Hardt Wolf-Dietrich
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
1540-9538
DOI
10.1084/jem.20070633
Published
2008-02-18
Epub
2008-00-11
Pages
437-50
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2271026
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20070633 PMC Full Text View journal details
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