Our research focuses on understanding how innate immune responses such as cell death, autophagy and inflammasome activity influence host defence against Mycobacterium tuberculosis (Mtb). We have found that Mtb replicates in alveolar macrophages and dendritic cells (DCs) helped, in part, by its ability to subvert protective host responses such as apoptosis and autophagy. We are also characterizing the effect of ESAT-6, an Mtb virulence factor and putative vaccine candidate, on macrophage function. A better understanding of these host-pathogen interactions may allow us to identify and develop new strategies for the treatment and prevention of TB.
Inhalable therapies have been proposed as an adjunct to conventional chemotherapy for TB with the potential to reduce systemic toxicity and the duration of treatment. With our collaborator Dr Sally-Ann Cryan in the School of Pharmacy, RCSI we have found that phagocytosis of PLGA microparticles by macrophages activates protective innate immune responses including NFkB activation and cytokine secretion and may enhance the efficacy of microencapsulated anti-mycobacterial drugs in the lung.
High Content Analysis of LC3 positive autophagic puncta (green) in uninfected macrophages and macrophages infected with M. tuberculosis. The plasma membrane is stained red and the nuclei are stained blue.
For further information about Dr Mary O'Sullivan please view her CV Profile.