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

doi:10.1038/ncomms13180

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

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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, …

Nature communications, Vol.7(1), pp.13180-13180

10/25/2016

DOI: 10.1038/ncomms13180

PMCID: PMC5093323

PMID: 27779193

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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.

Details

Title: Subtitle: Nlrp12 mutation causes C57BL/6J strain-specific defect in neutrophil recruitment
Creators: Tyler K Ulland - Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Nidhi Jain - Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
Emma E Hornick - Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Eric I Elliott - Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Gwendolyn M Clay - Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Jeffrey J Sadler - Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Kathleen A M Mills - Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Ann M Janowski - Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
A Paige Davis Volk - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Kai Wang - Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa 52242, USA
Kevin L Legge - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Lokesh Gakhar - Protein Crystallography Facility, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Mohammed Bourdi - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Polly J Ferguson - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Mary E Wilson - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Suzanne L Cassel - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Fayyaz S Sutterwala - Veterans Affairs Medical Center, Iowa City, Iowa 52246, USA
Resource Type: Journal article
Publication Details: Nature communications, Vol.7(1), pp.13180-13180
DOI: 10.1038/ncomms13180
PMID: 27779193
PMCID: PMC5093323
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: England
Grant note: T32 AI007517 / NIAID NIH HHS P30 ES005605 / NIEHS NIH HHS R01 AI118719 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS T32 GM007337 / NIGMS NIH HHS I01 BX000536 / BLRD VA P01 AI044642 / NIAID NIH HHS R01 AR059703 / NIAMS NIH HHS R01 AI104706 / NIAID NIH HHS R56 AI118719 / NIAID NIH HHS U54 AI057160 / NIAID NIH HHS T32 CA009547 / NCI NIH HHS
Language: English
Date published: 10/25/2016
Academic Unit: Microbiology and Immunology; International Programs; Stead Family Department of Pediatrics; Epidemiology; Pathology; Biostatistics; Radiation Research Laboratory; Rheumatology, Allergy, and Immunology; Biochemistry and Molecular Biology; Medicine Administration; Internal Medicine
Record Identifier: 9984001201002771

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