title: Cutting edge: Mouse NAIP1 detects the type III secretion system needle protein.
abstract: The NAIP/NLRC4 inflammasomes activate caspase-1 in response to bacterial type III secretion systems (T3SSs). Inadvertent injection of the T3SS rod protein and flagellin into the cytosol is detected through murine NAIP2 and NAIP5/6, respectively. In this study, we identify the agonist for the orphan murine NAIP1 receptor as the T3SS needle protein. NAIP1 is poorly expressed in resting mouse bone marrow-derived macrophages; however, priming with polyinosinic-polycytidylic acid induces it and confers needle protein sensitivity. Further, overexpression of NAIP1 in immortalized bone marrow-derived macrophages by retroviral transduction enabled needle detection. In contrast, peritoneal cavity macrophages basally express NAIP1 and respond to needle protein robustly, independent of priming. Human macrophages are known to express only one NAIP gene, which detects the needle protein, but not rod or flagellin. Thus, murine NAIP1 is functionally analogous to human NAIP.
authors.affiliation: Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Manira
authors.initials: M
authors.lastname: Rayamajhi
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Zak
authors.forename: Joseph
authors.initials: J
authors.lastname: Chavarria-Smith
authors.forename: Russell E
authors.initials: RE
authors.lastname: Vance
authors.forename: Edward A
authors.initials: EA
authors.lastname: Miao
mesh_terms: D000818:Animals; D058947:Bacterial Secretion Systems / Q000276:immunology*; D001854:Bone Marrow Cells / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000819:agonists / Q000378:metabolism*; D011070:Poly I-C / Q000276:immunology
chemical_list: D058947:Bacterial Secretion Systems; C496801:Naip1 protein, mouse; D051616:Neuronal Apoptosis-Inhibitory Protein; D020170:Caspase 1; D011070:Poly I-C
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