title: Peptidoglycan Modifications Tune the Stability and Function of the Innate Immune Receptor Nod2.
abstract: Natural modifications of peptidoglycan modulate the innate immune response. Peptidoglycan derivatives activate this response via the intracellular innate immune receptor, Nod2. To probe how these modifications alter the response, a novel and efficient carbohydrate synthesis was developed to allow for late-stage modification of the amine at the 2-position. Modification of the carbohydrate was found to be important for stabilizing Nod2 and generating the proper response. The native Nod2 ligands demonstrate a significant increase in the cellular stability of Nod2. Moreover, changing the identity of the natural ligands at the carbohydrate 2-position allows for the Nod2-dependent immune response to be either up-regulated or down-regulated. The ligand structure can be adjusted to tune the Nod2 response, suggesting that other innate immune receptors and their ligands could use a similar strategy.
authors.affiliation: †Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: Melnyk
authors.affiliation: †Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States.
authors.forename: Vishnu
authors.initials: V
authors.lastname: Mohanan
authors.affiliation: †Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Schaefer
authors.affiliation: †Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Hou
authors.affiliation: †Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States.
authors.forename: Catherine Leimkuhler
authors.initials: CL
authors.lastname: Grimes
mesh_terms: D007113:Immunity, Innate; D053473:Nod2 Signaling Adaptor Protein / Q000737:chemistry*; D010457:Peptidoglycan / Q000737:chemistry*
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan