The importance of IL-33 in immunotolerance to filovirus infections in bats (BatFIM) (pilot project)

Bats are natural reservoirs of diverse viral zoonotic pathogens, including highly-pathogenic filoviruses like Marburg virus (MARV) and Ebola viruses, causative agents of viral hemorrhagic fevers in humans. The reservoir competence of bats depends on their ability to host viruses in the general absence of symptoms or pathology. One proposed mechanism for their reservoir competence is “immunotolerance”, involving tightly controlled anti-viral immune responses and suppressed pro-inflammatory signalling.

In mammals, myeloid cells like dendritic cells (DC) and macrophages (Mph) are professional antigen presenting cells (APCs), which dictate host immune responses to infection. Both DC and Mph are also key initial targets of filoviruses. Importantly, filovirus infections typically cause disrupted cell responses of human DC and Mph. In contrast, bat DCs from the natural MARV reservoir R. aegyptiacus were recently shown to initiate prominent anti-viral immune responses against MARV and significantly suppress proinflammatory responses like the cytokine IL-33. Whether bat Mph display similarly suppressed IL-33 responses as bat DCs and whether human myeloid cells show a contrasting 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 bat versus human DC and Mph IL-33 responses to MARV and EBOV in vitro, therefore offering a unique first opportunity to understand the underlying differences in human and bat immune cell responses to two of the most highly-pathogenic viral zoonoses.

Contact:

Dr. Ivet A. Yordanova

Centre for Biological Threats and Special Pathogens, Robert Koch Institute