An Anti-Inflammatory Role for NLRP10 in Murine Cutaneous Leishmaniasis

作者：Clay Gwendolyn M; Valadares Diogo G; Graff Joel W; Ulland Tyler K; Davis Richard E; Scorza Breanna M; Zhanbolat Bayan Sudan; Chen Yani; Sutterwala Fayyaz S; Wilson Mary E^*

来源：The Journal of Immunology, 2017, 199(8): 2823-2833.

DOI：10.4049/jimmunol.1500832

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.

• 出版日期2017-10-15