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

Immunobiology. 2016 Feb;221(2):341-6. doi: 10.1016/j.imbio.2015.10.001. Epub 2015 Oct 23.


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.

Keywords: Inflammation; Migration; NLRP12; Neutrophils; TLR signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Movement / immunology*
  • Chemokine CXCL1 / genetics
  • Chemokine CXCL1 / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / parasitology
  • Female
  • Gene Expression Regulation
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Leishmania major / immunology
  • Lipopolysaccharides / pharmacology
  • Macrophages / immunology
  • Macrophages / parasitology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / immunology
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / immunology
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Neutrophils / immunology*
  • Neutrophils / parasitology
  • Organ Specificity
  • Signal Transduction


  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • NF-kappa B
  • NLRP12 protein, mouse
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3