title: Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands.
abstract: Muramyl peptides are the building blocks of bacterial peptidoglycan, and their biological functions in mammals have been extensively studied. In particular, muramyl peptides trigger inflammation, contribute to host defense against microbial infections, and modulate the adaptive immune response to antigens. These bacterial molecules are detected by nucleotide oligomerization domain 1 (Nod1) and Nod2, and recent evidence suggests that muramyl dipeptide also activates NLRP3 and NLRP1 inflammasomes. Here, we investigated the role of Rip2, the adaptor for Nod1- and Nod2-dependent signaling, in multiple aspects of the host response to muramyl peptides in vivo, such as inflammatory cytokine secretion, activation and recruitment of macrophages and neutrophils to the site of injection, systemic activation of myeloid, T and B cells in the spleen, adjuvanticity and capacity to polarize the adaptive response to ovalbumin. Our results demonstrate that Rip2 was crucial for all the biological functions studied. We also identified CD11c(int) CD11b(+) inflammatory dendritic cells as a major myeloid cell population responding to Nod stimulation in vivo. Together, our results highlight the importance of Rip2 for Nod-dependent induction of innate and adaptive immunity.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Joao G
authors.initials: JG
authors.lastname: Magalhaes
authors.forename: Jooeun
authors.initials: J
authors.lastname: Lee
authors.forename: Kaoru
authors.initials: K
authors.lastname: Geddes
authors.forename: Stephen
authors.initials: S
authors.lastname: Rubino
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Girardin
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology*; D056704:Adaptive Immunity; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D039481:CD11b Antigen / Q000235:genetics; D039521:CD11c Antigen / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D007113:Immunity, Innate; D058847:Inflammasomes; D007249:Inflammation / Q000276:immunology; D008024:Ligands; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D053474:Nod1 Signaling Adaptor Protein / Q000276:immunology* / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D039481:CD11b Antigen; D039521:CD11c Antigen; D058847:Inflammasomes; D008024:Ligands; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D010047:Ovalbumin; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse