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The duck inflammasome is not activated by nigericin

2021 CPRF
The NOD-like receptor protein 3 (NLRP3) inflammasome is part of the innate immune system that induces pro-inflammatory responses and pyroptosis, a form of cell death. The NLRP3 inflammasome responds to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). The NLRP3 inflammasome consists of 3 components: NLRP3, the apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 (CASP1). Inflammasome activation leads to the activation of IL-1β, a pro-inflammatory cytokine. The NLRP3 inflammasome plays a role in innate immune defense against avian influenza virus (IAV) but also contributes to the immunopathology caused by IAV infections. Leading to a dysregulated release of pro-inflammatory cytokines known as a cytokine storm in areas of infection—namely, the lungs, NLRP3 inflammasome activation can lead to deleterious outcomes for the host. The NLRP3 inflammasome is currently uncharacterized in many bird species, including ducks. Ducks are the natural reservoir host of IAV and are resistant to highly pathogenic strains which have devastating effects on other species. Because ducks are resistant to IAV, characterizing the duNLRP3 inflammasome is of interest to us. Using transcriptomics and bioinformatics, duNLRP3, duCASP1, and duIL-1β have been identified but it does not appear that ducks have ASC, indicating that the duNLRP3 inflammasome does not have the same function as known mammalian ones. Through qPCR, gene expression of duNLRP3 inflammasome in duck embryonic fibroblasts after treatment with nigericin, a known NLRP3 inflammasome agonist, show that NLRP3, CASP1, and IL-1β are not upregulated. Confocal microscopy of co-transfected duNLRP3, duCASP1, and duIL-1β constructs in chicken embryonic fibroblasts (DF-1s) show inconsistent co-localization of these three proteins. Western blots show that protein expression decreased during co-transfections compared to single construct transfections, suggesting that cell death may be occurring in successfully co-transfected cells. In the future, I will use the tagged duck proteins to examine whether different PB1-F2, an IAV protein, shown to increase pathogenesis by increasing inflammation, can activate the duNLRP3 inflammasome. Characterizing the duck NLRP3 inflammasome and its response allows us to better understand whether avoiding inflammasome activation is a strategy by which the ducks avoid damage from IAV.
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MSc Student

University of Alberta

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