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

2016; Nature Portfolio; Volume: 7; Issue: 1 Linguagem: Inglês

10.1038/ncomms13180

2041-1723

Tyler K. Ulland, Nidhi Jain, Emma E. Hornick, Eric I. Elliott, Gwendolyn Clay, Jeffrey J. Sadler, K. 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,

Immune Cell Function and Interaction

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.