Gation. Colonoscopy was performed making use of a flexible digital ureteroscope on the day 7 of DSS remedy. To get a complete description, see SI Supplies and Approaches. BM Chimeric Mice. Mice receiving BM transfer have been irradiated (900 radiation absorbed dose) quickly prior to transplantation. BM was harvested from femurs and tibias of 4-wk-old SAMP or AKR mice. To get a complete description, see SI Supplies and Strategies. Myeloperoxidase Assay Activity. Colon samples were assayed for myeloperoxidase (MPO) activity as previously S1PR3 Compound described (31, 32). For any complete description, see SI Components and Techniques. Salmonella Infection Assays. Salmonella infection assays had been performed as previously described (9). For a full description, see SI Materials and Techniques. Salmonella Infection in Vivo. SAMP and AKR handle mice (four wk) had been infected with Salmonella for 2 d. For any complete description, see SI Materials and Strategies. Statistical Evaluation. Analyses of continuous data were conducted utilizing parametric Student t tests, one-way or two-way ANOVAs, or linear regression (when proper), or their nonparametric options. For a full description, see SI Supplies and Techniques. ACKNOWLEDGMENTS. We thank Prof. Maria Grazia Cifone (University of L’Aquila) for scientific help; Dr. Marcello Chieppa for assistance with bone marrow chimeric mice; Dr. Amitabh Chak for support together with the mouse colonoscopy; and Li-Guo Jia, Mitchell Guanzon, Dennis Gruszka, Sarah Kossak, Lindsey Kaydo, and Homer Craig for their technical support. This work was supported by National Institutes of Overall health Grants DK091222 (to F.C.), DK055812 (to F.C.), DK042191 (to F.C. and T.T.P.), and DK082437 (to C.M.), too because the Howard Hughes Health-related Institute “Med into Grad” Initiative.1. Gutierrez O, et al. (2002) Induction of Nod2 in myelomonocytic and intestinal epithelial cells through nuclear factor-kappa B activation. J Biol Chem 277(44):417011705. two. Girardin SE, et al. (2003) Nod2 can be a common sensor of peptidoglycan by means of muramyl dipeptide (MDP) detection. J Biol Chem 278(11):8869872. 3. Inohara N, et al. (2003) Host recognition of bacterial muramyl dipeptide mediated via NOD2. Implications for Crohn’s disease. J Biol Chem 278(eight):5509512. four. Inohara N, Nu z G (2003) NODs: Intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol three(five):37182. 5. Kim JY, Omori E, Matsumoto K, N��ez G, Ninomiya-Tsuji J (2008) TAK1 is actually a central mediator of NOD2 signaling in epidermal cells. J Biol Chem 283(1):13744. 6. Park JH, et al. (2007) RICK/RIP2 mediates innate immune responses induced by way of Nod1 and Nod2 but not TLRs. J Immunol 178(four):2380386. 7. Wagner CS, Cresswell P (2012) TLR and nucleotide-binding oligomerization domain-like receptor signals differentially regulate exogenous antigen presentation. J Immunol 188(two): 68693. 8. Cooney R, et al. (2010) NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 16(1):907. 9. Homer CR, Richmond AL, Rebert NA, Achkar JP, McDonald C (2010) ATG16L1 and NOD2 interact in an autophagy-dependent antibacterial pathway implicated in Crohn’s PI3Kβ custom synthesis illness pathogenesis. Gastroenterology 139(five):1630641. ten. Hampe J, et al. (2001) Association between insertion mutation in NOD2 gene and Crohn’s illness in German and British populations. Lancet 357(9272):1925928. 11. Hugot JP, et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s illness. Nature 411(6837):59903. 12. Ogu.