A study suggests molecular mechanisms that allow bats to tolerate zoonotic viruses. Bats act as reservoirs of numerous zoonotic viruses, including SARS-CoV, MERS-CoV, Ebola virus, and, possibly, SARS-CoV-2, the pathogen behind the ongoing coronavirus pandemic. However, the array of molecular mechanisms bats deploy to tolerate pathogenic viruses remains unclear. Aaron Irving, Lin-Fa Wang, and colleagues report that a lack of AIM-2 receptors--pattern-recognizing immune receptors that sense intracellular DNA of pathogenic origin and trigger a cascade of events culminating in inflammation and cell death--in bats' genomes might help tamp down bats' inflammasome signaling pathway and sustain a viral reservoir. In vitro experiments in which genes for the human AIM2 receptor were introduced into bat kidney and immune cells resulted in partial restoration of inflammasome signaling, producing aggregates that mark the onset of an inflammatory response. Additionally, in black fruit bats (Pteropus alectco), the authors found reduced activity of the enzyme caspase-1, a key player in inflammasome signaling that triggers maturation and release of the cytokine IL-1β, which in turn helps mobilize immune defense. Dampened caspase-1 activity was likely due to a pair of amino acid substitutions at positions 365 and 371 of the bat enzyme, compared with the corresponding mouse and human enzymes. Further, the authors identified a mechanism that balances caspase-1 activity and IL-1β maturation in a complementary manner in three bat species--P. alecto, Eonycteris spelaea (cave nectar bat), and Myotis davidii (David's myotis)--to dampen inflammasome signaling and curtail the immune response. According to the authors, the findings suggest that bats have coopted different strategies, reducing caspase-1 activation, hampering IL-1β maturation, or both, to blunt immune responses against zoonotic viruses.
Article #20-03352: "Complementary regulation of caspase-1 and IL-1β reveals additional mechanisms of dampened inflammation in bats," by Geraldine Goh, Matae Ahn, et al.
MEDIA CONTACT: Lin-Fa Wang, Duke-National University of Singapore Graduate Medical School, SINGAPORE; e-mail: linfa.wang@duke-nus.edu.sg
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Proceedings of the National Academy of Sciences