Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Characterization of Inflammasomes and Their Regulation in the Red Fox

Version 1 : Received: 28 November 2023 / Approved: 28 November 2023 / Online: 28 November 2023 (07:29:31 CET)

A peer-reviewed article of this Preprint also exists.

Ahn, H.; Jeong, D.-H.; Lee, G.; Lee, S.-J.; Yang, J.-J.; Kim, Y.-H.; Hahn, T.-W.; Choi, S.; Lee, G.-S. Characterization of Inflammasomes and Their Regulation in the Red Fox. Animals 2023, 13, 3842. Ahn, H.; Jeong, D.-H.; Lee, G.; Lee, S.-J.; Yang, J.-J.; Kim, Y.-H.; Hahn, T.-W.; Choi, S.; Lee, G.-S. Characterization of Inflammasomes and Their Regulation in the Red Fox. Animals 2023, 13, 3842.

Abstract

Background: Inflammasomes recognize cytosolic danger signals, including pathogens, and subsequently induce the secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β. Studying inflammasomes in the red fox (Vulpes vulpes) is crucial from a wildlife veterinary and public health perspective, as it can be used to help control and prevent the transmission of zoonotic pathogens. The understanding of how diversity in inflammasomes across species affects pathogen carriage in the red fox is still limited. Methods: We investigated the activation and intracellular mechanisms of three inflammasomes (NLRP3, AIM2, and NLRC4) in fox peripheral blood mononuclear cells (PBMCs), using established triggers and inhibitors derived from humans and mice. Results: Fox PBMCs exhibited normal activation and induction of IL-1β secretion in response to representative inflammasome triggers (ATP and nigericin for NLRP3, dsDNA for AIM2, flagellin for NLRC4). However, in inhibitor studies, MCC950, a selective NLRP3 inhibitor, suppressed IL-1β secretion mediated by the fox AIM2 and NLRC4 inflammasomes. Conclusions: These findings suggest that NLRP3 may have a common role in dsDNA- and flagellin-mediated inflammasome activation in the red fox. In conclusion, this fox inflammasome biology can be applied to the control of zoonotic infections and the treatment of inflammasome-mediated diseases in the red fox.

Keywords

Red foxes; Vulpes vulpes; inflammasome; cytokine; interleukin-1beta

Subject

Biology and Life Sciences, Animal Science, Veterinary Science and Zoology

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