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

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

Ulland TK1,2, Jain N1,3, Hornick EE1,4, Elliott EI1,2,3,5, Clay GM2,5, Sadler JJ1, Mills KA1, Janowski AM1,4, Volk AP1,6, Wang K7, Legge KL4,5,8, Gakhar L9,10, Bourdi M11, Ferguson PJ6, Wilson ME2,4,5,12,13,14, Cassel SL1,3,4,12, Sutterwala FS1,2,3,4,5,12,13.

Author information

1
Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
2
Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
3
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
4
Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
5
Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
6
Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
7
Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa 52242, USA.
8
Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
9
Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
10
Protein Crystallography Facility, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
11
Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
12
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
13
Veterans Affairs Medical Center, Iowa City, Iowa 52246, USA.
14
Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.

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.

PMID:
27779193
PMCID:
PMC5093323
DOI:
10.1038/ncomms13180
[Indexed for MEDLINE]
Free PMC Article

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