Abstract
Abstract Previous studies have indicated the importance of Nod-like receptor pyrin containing domain 3 (NLRP3) to early immune response in St. Croix (STC) sheep. NLRP3 is important to Th2 immune response, which is the classical response to Haemonchus contortus larval antigen (HcLA). Th2 response is driven by interleukin (IL) -4 and IL-13 cytokine production and early production prevents parasite establishment and further resistance as seen in STC response to LPS, classical NLRP3 activation. Distinct differences have been seen in the structure of NLRP3 between both STC and SUF. STC upregulates inflammatory genes NLRP3, TLR4 and TLR2 in response to LPS, while SUF showed delayed responses leading to their susceptibility. The objective of this study was to investigate the role of NLRP3 in differential breed response, in the context of Hc infection. P Peripheral blood mononuclear cells (PBMC) from both SUF and STC were isolated and stimulated with HcLA antigen only, HcLA antigen in combination with pharmacological inhibitor of NLRP3 (MCC950) and complete media for 6 hours. Gene expression revealed that treatment with MCC950 upregulated TLR2 (P < 0.001), TLR4 (P < 0.001), STAT6 (P < 0.001), IL-4 and IL-10 (P < 0.001) in SUF PBMC while STC showed an increase in IL-1β (P < 0.001). This indicates that inhibition of NLRP3 improves response of SUF to Hc antigen and confirms importance of NLRP3 to immune response in STC.
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