Bat-FIM - The role of IL33 Signaling for the immune tolerance against filovirus-infection in Bats.

Bats are natural reservoirs for several viral zoonotic agents, including highly pathogenic filoviruses such as Marburg virus (MARV) and Ebola virus, the causative agents of viral hemorrhagic fever in humans. The reservoir competence of bats depends on their ability to harbor viruses without symptoms or pathology. One proposed mechanism for their reservoir competence is "immune tolerance," which involves a tightly controlled antiviral immune response and suppressed proinflammatory signaling. In mammals, myeloid cells such as dendritic cells (DC) and macrophages (Mph) are professional antigen-presenting cells (APC) that control the host immune response to infection. Both DC and Mph are also important initial targets of filoviruses. Importantly, filovirus infections lead to disruption of cell responses of human DC and Mph. In contrast, bat DCs from the natural MARV reservoir R. aegyptiacus were recently shown to elicit a distinct antiviral immune response against MARV and significantly suppress proinflammatory responses such as the cytokine IL-33. Whether bat Mph exhibit a similarly suppressed IL-33 response as bat DCs and whether, in contrast, human myeloid cells exhibit increased IL-33 release following infection with MARV or EBOV is unknown. This project therefore aims to differentiate bat-derived Mph from two known bat reservoirs of filoviruses and to compare for the first time the IL-33 responses of bat DCs and Mphs to MARV and EBOV in vitro with those of humans, providing a unique opportunity to understand the underlying differences in immune cell responses of humans and bats to two of the highly pathogenic viral zoonoses.