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

Tyler K. Ulland, Nidhi Jain, Emma E. Hornick, Eric I. Elliott, Gwendolyn M. Clay, Jeffrey J. Sadler, Kathleen A.M. Mills, Ann M. Janowski, A. Paige Davis Volk, Kai Wang, Kevin L. Legge, Lokesh Gakhar, Mohammed Bourdi, Polly J. Ferguson, Mary E. Wilson, Suzanne L. Cassel, Fayyaz S. Sutterwala

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Article number13180
JournalNature communications
Volume7
DOIs
StatePublished - Oct 25 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Ulland, T. K., Jain, N., Hornick, E. E., Elliott, E. I., Clay, G. M., Sadler, J. J., Mills, K. A. M., Janowski, A. M., Volk, A. P. D., Wang, K., Legge, K. L., Gakhar, L., Bourdi, M., Ferguson, P. J., Wilson, M. E., Cassel, S. L., & Sutterwala, F. S. (2016). Nlrp12 mutation causes C57BL/6J strain-specific defect in neutrophil recruitment. Nature communications, 7, [13180]. https://doi.org/10.1038/ncomms13180