Investigating the role of macrophage and monocyte heterogeneity in influenza induced lung pathogenesis

Macrophages and monocytes are part of the early innate immune response to influenza. It is now well-established that residential tissue macrophages exert differential immunoregulatory functions to pro-inflammatory monocytes recruited from the bloodstream. Using a combination of transcriptome studies and targeted genomic engineering, we are now investigating the specific immunoregulatory proteins facilitating macrophage and monocyte mediated immune responses against influenza, with the key goal of identifying new and translatable protective therapeutic targets against influenza infection as well as pathological biomarkers of enhanced disease severity in human patients. As macrophages play a central role in immune cell homeostasis in the lungs, we are also investigating the role of macrophages and monocytes in either enhancing or suppressing anti-influenza CD8 T cell immunity.

We are also expanding our development of lung disease immunophenotyping panels (Duan et al, Mucosal Immunology, 2015) to identify chronic lung disease patient subpopulations with elevated risks of developing severe influenza induced pneumonia. This study will enable us to elucidate the underlying innate immune cell mechanisms masking heterogeneous recovery responses to influenza infections in the human population.