Triggers of NLRC4 and AIM2 inflammasomes induce porcine IL-1β secretion.

Abstract

Pigs are an important livestock and serve as a large animal model due to physiological and anatomical similarities with humans. Thus, components of the porcine immune system such as inflammasomes need to be characterized for disease control, vaccination, and translational research purposes. Previously, we and others elucidated porcine nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family Pyrin domain containing 3 (NLRP3) inflammasome activation. However, until now, porcine NLR family caspase recruitment domain (CARD)-containing 4 (NLRC4) and absent in melanoma 2 (AIM2) inflammasomes have been not well studied. In this study, we treated well defined NLRC4 and AIM2 inflammasome triggers to porcine peripheral blood mononuclear cells (PBMCs) and murine bone-marrow derived macrophages (BMDMs) and observed interleukin (IL)-1β maturation as a readout of inflammasome activation. NLRC4 (flagellin) and AIM2 (dsDNA) triggers led to IL-1β secretion in both porcine PBMCs and mice macrophages. In addition, porcine and mouse NLRC4 and AIM2 inflammasomes responded differently to NLRP3 inhibitors. Bacterial inflammasome triggers, Salmonella enterica serovar Typhimurium, Listeria monocytogenes, and Escherichia coli, also induced IL-1β secretion in porcine PBMCs. Taken together, we suggest that known triggers of NLRC4 and AIM2 inflammasomes in mice induce IL-1β secretion in porcine PBMCs.