Complementary regulation of caspase-1 and IL-1β reveals additional mechanisms of dampened inflammation in bats
Geraldine Goh, Matae Ahn, Feng Zhu, Lim Beng Lee, Dahai Luo, Aaron T. Irving, Lin‐Fa Wang
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.