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

Hapfelmeier, Siegfried; 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 (2008). Microbe sampling by mucosal dendritic cells is a discrete, MyD88-independent step in DeltainvG S. Typhimurium colitis. The Journal of experimental medicine, 205(2), pp. 437-450. Rockefeller Univ. Press 10.1084/jem.20070633

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research

UniBE Contributor:

Hapfelmeier, Siegfried Hektor

ISSN:

1540-9538

Publisher:

Rockefeller Univ. Press

Language:

English

Submitter:

Siegfried Hektor Hapfelmeier-Balmer

Date Deposited:

04 May 2015 14:29

Last Modified:

26 Jun 2016 02:01

Publisher DOI:

10.1084/jem.20070633

Related URLs:

PubMed ID:

18268033

Additional Information:

Notes: PMC2271026 Custom 1: papers3://publication/uuid/33A0CF34-C34F-4A0F-B324-60DAA1A1645B Date: 2008

BORIS DOI:

10.7892/boris.67829

URI:

https://boris.unibe.ch/id/eprint/67829

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