Abstract

Viral infections are increasing, remain difficult to treat and represent an urgent public health problem globally. A better understanding of the molecular mechanisms underlying innate immune responses to viral infections is at the heart of any control strategy. Excessive activation of the inflammatory response can lead to the phenomenon known as “cytokine storm” in which the uncontrolled and massive production of pro-inflammatory mediators becomes harmful to the body. Similarly, regulated cell death represents on one hand a fundamental defense mechanism, on the other a risk for the host. In fact, the type of cell death is an important factor in determining the outcome of the inflammatory response. To date, it is not clear what are the immunosensors responsible for triggering cell death during viral infections. This project aims at clarifying: 1) the role of intracellular viral nucleic acid recognition receptors (e.g. TLR3, MDA5 and RigI) in programmed cell death and in the production of type I interferon in human primary macrophages; 2) the role of caspases activated upon viral recognition; 3) the effector mechanisms of cell death with particular attention to gasdermins and MLKL.

Pipeline