Complementary regulation of caspase-1 and IL-1ß reveals additional mechanisms of dampened inflammation in bats

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Publication Date

11-17-2020

Publication Title

PNAS

Volume Number

117

Issue Number

46

Abstract

Significance Bats have been shown to dampen several key upstream pathogen and danger-associated molecular patterns, yet much of the downstream signaling is yet unknown. Here, we identify residues in caspase-1 which are critical for enzymatic activity and have been targeted for inhibition in Pteropus bats. Further, we discover cleavage-site flanking residues which lead to loss of IL-1β cleavage in Myotis bats. Thus, we report an inverse relationship between caspase-1 function and IL-1β cleavage, resulting in a consistent reduction of downstream signaling by the inflammasome across bats within the two suborders. In sum, we confirm that bats have targeted the inflammasome pathway at multiple levels and via heterogeneous strategies to reduce proinflammatory responses, thus mitigating potential immune-mediated tissue damage and disease.

Document Type

Article

Digital Object Identifier (DOI)

https://doi.org/10.1073/pnas.2003352117

Language

English

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