Nlrp12 mutation causes C57BL/6J strain-specific defect in neutrophil recruitment

Nat Commun. 2016 Oct 25;7:13180. doi: 10.1038/ncomms13180.

Abstract

The inbred mouse strain C57BL/6J is widely used in models of immunological and infectious diseases. Here we show that C57BL/6J mice have a defect in neutrophil recruitment to a range of inflammatory stimuli compared with the related C57BL/6N substrain. This immune perturbation is associated with a missense mutation in Nlrp12 in C57BL/6J mice. Both C57BL/6J and NLRP12-deficient mice have increased susceptibility to bacterial infection that correlates with defective neutrophil migration. C57BL/6J and NLRP12-deficient macrophages have impaired CXCL1 production and the neutrophil defect observed in C57BL/6J and NLRP12-deficient mice is rescued by restoration of macrophage NLRP12. These results demonstrate that C57BL/6J mice have a functional defect in NLRP12 and that macrophages require NLRP12 expression for effective recruitment of neutrophils to inflammatory sites.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Cell Movement
  • Chemokine CXCL1 / deficiency
  • Chemokine CXCL1 / genetics*
  • Chemokine CXCL1 / immunology
  • Disease Susceptibility
  • Francisella tularensis / immunology
  • Gene Expression
  • Immunity, Innate
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / immunology
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mutation*
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / pathology*
  • Survival Analysis
  • Tularemia / genetics
  • Tularemia / immunology*
  • Tularemia / microbiology
  • Tularemia / mortality

Substances

  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • NLRP12 protein, mouse