Project description:Bats as the only flying mammals incur a high metabolic cost during extended powered flight, which results in febrile-like temperatures without injury. Herein, we investigate the in vivo heat shock response (HSR) in the cave nectar bat Eonycteris spelaea. We demonstrate that E. spelaea exhibits enhanced physiological heat resistance, marked by reduced lethality, tissue damage and serum corticosterone levels in comparison to mice upon heat challenge. Additionally, E. spelaea did not exhibit an acute transcriptional response observed heat stress in mice. Instead, bats displayed a delayed and non-canonical HSR that did not involve the activation of classical heat shock related genes and pathways. This altered response in E. spelaea is attributed to the elevated basal expression of heat shock proteins, which we demonstrate to be a common characteristic exhibited by bats from diverse sub-orders, families and diets. Taken together, we demonstrate a distinct HSR in E. spelaea relative to the conventional model organism, mouse, which may provide insights to understand novel regulatory targets and effector proteins that underlie the mammalian heat shock response.
Project description:To examine the fundamental immunity in bats, particularly the status of their innate immune system in the basal healthy state, we profile Eonycteris spelaea bat tissue with Deep NGS coverage. This is coupled to a paired experiment where bats were stimulated in vivo with various PRR ligands to activate immune pathways.
Project description:Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigated the antiviral RNA interference (RNAi) pathway in bat cells and discovered that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs (vsiRNAs) upon Sindbis virus (SINV) infection that were missing in human cells. Disruption of Dicer function resulted in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors (PRRs), such as retinoic acid-inducible gene I (RIG-I), with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.
Project description:Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigated the antiviral RNA interference (RNAi) pathway in bat cells and discovered that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs (vsiRNAs) upon Sindbis virus (SINV) infection that were missing in human cells. Disruption of Dicer function resulted in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors (PRRs), such as retinoic acid-inducible gene I (RIG-I), with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.