Nod1 and Nod2 Regulation of Inflammation in the Salmonella Colitis Model

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2010 Oct 6

PMID 20921147

Citations 56

Authors

Kaoru Geddes

Stephen Rubino

Catherine Streutker

Joon Ho Cho

Joao G Magalhaes

Lionel Le Bourhis

Thirumahal Selvanantham

Stephen E Girardin

Dana J Philpott

Affiliations

Soon will be listed here.

Abstract

The pattern recognition molecules Nod1 and Nod2 play important roles in intestinal homeostasis; however, how these proteins impact on the development of inflammation during bacterial colitis has not been examined. In the streptomycin-treated mouse model of Salmonella colitis, we found that mice deficient for both Nod1 and Nod2 had attenuated inflammatory pathology, reduced levels of inflammatory cytokines, and increased colonization of the mucosal tissue. Nod1 and Nod2 from both hematopoietic and nonhematopoietic sources contributed to the pathology, and all phenotypes were recapitulated in mice deficient for the signaling adaptor protein Rip2. However, the influence of Rip2 was strictly dependent on infection conditions that favored expression of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (TTSS), as Rip2 was dispensable for inflammation when mice were infected with bacteria grown under conditions that promoted expression of the SPI-1 TTSS. Thus, Nod1 and Nod2 can modulate inflammation and mediate efficient clearance of bacteria from the mucosal tissue during Salmonella colitis, but their role is dependent on the expression of the SPI-2 TTSS.

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