title: NLRP12 is a neutrophil-specific, negative regulator of in vitro cell migration but does not modulate LPS- or infection-induced NF-κB or ERK signalling.
abstract: NOD-like receptors (NLR) are a family of cytosolic pattern recognition receptors that include many key drivers of innate immune responses. NLRP12 is an emerging member of the NLR family that is closely related to the well-known inflammasome scaffold, NLRP3. Since its discovery, various functions have been proposed for NLRP12, including the positive regulation of dendritic cell (DC) and neutrophil migration and the inhibition of NF-κB and ERK signalling in DC and macrophages. We show here that NLRP12 is poorly expressed in murine macrophages and DC, but is strongly expressed in neutrophils. Using myeloid cells from WT and Nlrp12(-/)(-) mice, we show that, contrary to previous reports, NLRP12 does not suppress LPS- or infection-induced NF-κB or ERK activation in myeloid cells, and is not required for DC migration in vitro. Surprisingly, we found that Nlrp12 deficiency caused increased rather than decreased neutrophil migration towards the chemokine CXCL1 and the neutrophil parasite Leishmania major, revealing NLRP12 as a negative regulator of directed neutrophil migration under these conditions.
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia 4072, Australia.
authors.forename: Alina
authors.initials: A
authors.lastname: Zamoshnikova
authors.affiliation: Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, and TUM Graduate School, Technische Universität München, 81675 Munich, Germany.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Groß
authors.affiliation: Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland; WHO-Immunology Research and Training Centre, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Steffen
authors.initials: S
authors.lastname: Schuster
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia 4072, Australia.
authors.forename: Kaiwen W
authors.initials: KW
authors.lastname: Chen
authors.affiliation: Ludwig Center for Cancer Research, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland; WHO-Immunology Research and Training Centre, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Tacchini-Cottier
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia 4072, Australia. Electronic address: K.Schroder@imb.uq.edu.au.
authors.forename: Kate
authors.initials: K
authors.lastname: Schroder
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D054360:Chemokine CXCL1 / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000469:parasitology; D005260:Female; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000469:parasitology; D009928:Organ Specificity; D015398:Signal Transduction
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C553199:NLRP12 protein, mouse; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Inflammation; Migration; NLRP12; Neutrophils; TLR signalling