Triggers of NLRC4 and AIM2 inflammasomes induce porcine IL-1β secretion
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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.
KeywordsPig Interleukin-1beta Macrophages NLRC4 AIM2
This research was supported by 2016 Research Grant from Kangwon National University (No. 520160446), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2015R1A2A2A01004183, NRF-2016R1A4A1010115, and NRF-2018R1A2B2004097).
Ahn, H. and Kim, J. and Lee, G.-S. designed the research; Ahn, H. Kim, J. and Kwon, S. performed the experiments; Ahn, H. Kwon, H.M., Kim, P.-H., Lee, E. and Lee, G.-S. analyzed the results; Ahn, H. Kim, J. and Lee, G.-S. wrote the paper; Kim, P.-H., Kwon, H.M., and Lee, E. edited and commented on the manuscript.
Compliance with ethical standards
The author has no conflict of interest to declare.
- van Hout GP et al (2016) The selective NLRP3-inflammasome inhibitor MCC950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction. Eur Heart J. https://doi.org/10.1093/eurheartj/ehw247
- Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith BL, Rajendiran TM, Nunez G (2013) K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38:1142–1153. https://doi.org/10.1016/j.immuni.2013.05.016 CrossRefPubMedPubMedCentralGoogle Scholar
- Tohno M, Shinkai H, Toki D, Okumura N, Tajima K, Uenishi H (2016) Identification of the Q969R gain-of-function polymorphism in the gene encoding porcine NLRP3 and its distribution in pigs of Asian and European origin. Immunogenetics 68:693–701. https://doi.org/10.1007/s00251-016-0917-y CrossRefPubMedGoogle Scholar