Mathematical Analysis of Receptor-Mediated Immune Cell Death in Antiviral Immunity
Respiratory diseases caused by influenza virus are an ongoing worldwide challenge for public health. Hence, understanding the viral replication mechanism and the interactions between the virus and the immune response is critical to prevent future influenza pandemics. Recently, regulation of the death receptor pathway in natural killer (NK) cells was targeted experimentally to study the role of apoptosis (programmed cell death) during Influenza A virus (IAV) infection. By increasing the expression level of c-FLIP (a key regulator of signaling complexes downstream of death receptors) which results in longer lifespan NK cells, a higher viral load was observed compared to wild-type mice. Furthermore, experiments showed that NK cells can get infected by IAV.
We propose different mathematical models to provide a quantitative understanding of the role of apoptosis mediated death in NK cells. The results show that infection of NK cells with a longer lifespan alone cannot explain the observed high viral load. Our working hypothesis is that the lack of caspase 3 due to overexpression of c-FLIP may contribute to higher virus production in NK cells.
Sahamoddin Khailaie, Michael Meyer-Hermann
- System-Immunologie- Prof. Dr. Michael Meyer-Hermann