Dr Nikhil Vergis, Co-Investigator
Functional and phenotypic characteristics of peripheral blood cells will be assessed using fluorescence-activated cell sorting techniques.
Detailed characterisation of the immunophenotype and antimicrobial responses of circulating myeloid cell populations will be performed at baseline and at subsequent defined timepoints following admission as outlined above. Briefly, functional immune readouts will assess pathogen clearance capabilities (e.g. phagocytosis, bacterial killing), innate (e.g. toll-like receptor) and adaptive (antigen independent evoked T cell responses-allogeneic mixed lymphocyte reaction) responses to microbial cues. Using ex-vivo and in vitro strategies, we will subsequently test the impact of the therapeutic strategies/agents on anti-microbial responses of circulating myeloid cells.
Monocyte and lymphocyte profiles identified above will be used in future studies, including the ISAIAH and MAFIA trials to assess the impact of novel pharmaceutical interventions on the susceptibility to infection. In addition we will use stored monocytes from AH patients to assess ex-vivo responses to cytokine manipulation and other therapeutic approaches to determine whether novel therapies are likely to increase infection risk. As an exploratory proof-of-principal we will work with GSK to profile monocyte responses to BET inhibitors.