An Anti-Inflammatory Role for NLRP10 in Murine Cutaneous Leishmaniasis.

The role of the nucleotide-binding domain and leucine-rich repeat containing receptor NLRP10 in disease is incompletely understood. Using three mouse strains lacking the gene encoding NLRP10, only one of which had a coincidental mutation in DOCK8, we documented a role for NLRP10 as a suppressor of the cutaneous inflammatory response to Leishmania major infection. There was no evidence that the enhanced local inflammation was due to enhanced inflammasome activity. NLRP10/DOCK8-deficient mice harbored lower parasite burdens at the cutaneous site of inoculation compared with wild-type controls, whereas NLRP10-deficient mice and controls had similar parasite loads, suggesting that DOCK8 promotes local growth of parasites in the skin, whereas NLRP10 does not. NLRP10-deficient mice developed vigorous adaptive immune responses, indicating that there was not a global defect in the development of Ag-specific cytokine production. Bone marrow chimeras showed that the anti-inflammatory role of NLRP10 was mediated by NLRP10 expressed in resident cells in the skin rather than by bone marrow-derived cells. These data suggest a novel role for NLRP10 in the resolution of local inflammatory responses during L. major infection. Copyright © 2017 by The American Association of Immunologists, Inc.

Citation

Gwendolyn M Clay, Diogo G Valadares, Joel W Graff, Tyler K Ulland, Richard E Davis, Breanna M Scorza, Bayan Sudan Zhanbolat, Yani Chen, Fayyaz S Sutterwala, Mary E Wilson. An Anti-Inflammatory Role for NLRP10 in Murine Cutaneous Leishmaniasis. Journal of immunology (Baltimore, Md. : 1950). 2017 Oct 15;199(8):2823-2833

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PMID: 28931602

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