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Project

Understanding the role of neutrophil recruitment and activation in arboviral diseases

As first cells recruited to inflammatory sites, neutrophils restrain infections, but also cause excessive tissue destruction and immunopathology. Neutrophils are known to be crucial to clear bacterial pathogens, but their contribution to host defense and response to viral diseases, e.g. arbovirus-induced encephalitis or arthritogenic disease are much less understood. Indeed, seen as secondary players in viral infection control, the role of neutrophils in development, severity and resolution of viral encephalitis has been neglected. Molecules involved in neutrophil recruitment and invasion of the central nervous system remain unclear, as are the effector mechanisms unleashed by neutrophils when encountering infected and damaged cells. We will investigate in detail the effects of arboviral infections on neutrophil recruitment and activation and correlate neutrophil activity in tissue to disease severity. Our approach will combine models of infection with St. Louis encephalitis virus and Mayaro virus and advanced techniques such as intravital microscopy to evaluate the inflammatory milieu in tissues. We will identify the chemokines and adhesion molecules driving neutrophil infiltration, activation and viral clearance. Neutrophil effector mechanisms will be investigated with pharmacological inhibitors or using knock-out mice. This project will uncover the role of neutrophils in neglected arboviral diseases and propose new strategies to control disease severity and inflammatory damage.

Date:27 Sep 2021 →  Today
Keywords:neutrophil granulocyte, arbovirus
Disciplines:Inflammation, Innate immunity, Infectious diseases, Virology
Project type:PhD project