Open AccessNod1 and Nod2 Regulation of Inflammation in the Salmonella Colitis Model
Author(s) -
Kaoru Geddes,
Stephen Rubino,
Catherine Streutker,
Joon Ho Cho,
Joao G. Magalhães,
Lionel Le Bourhis,
Thirumahal Selvanantham,
Stephen E. Girardin,
Dana J. Philpott
Publication year - 2010
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00759-10
Subject(s) - nod1 , nod2 , colitis , inflammation , salmonella , biology , immunology , microbiology and biotechnology , immune system , innate immune system , bacteria , genetics
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 ofSalmonella 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 theSalmonella 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 duringSalmonella colitis, but their role is dependent on the expression of the SPI-2 TTSS.