Metabolic profiling of endoplasmic reticulum stress in TB infected cells Mohanapriya Kumaran, Fred Quinn Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia 4168

Abstract Description The molecular mechanisms involved in the pathogenesis of Mycobacterium tuberculosis (M.tb) infection are still not clearly defined. M.tb interacts with various cell types during the initial stages of infection, the most important being alveolar macrophages (AMs). AMs are potent phagocytes with distinct metabolic and molecular characteristics, combining properties of both M1 and M2 macrophage phenotypes. Endoplasmic reticulum stress response (ERS) is very well characterized in tuberculosis (TB). ERS mediated apoptosis is important to neutralize phagocytosed Mycobacteria and ERS itself manifests differently in various macrophages. For example, ERS mediated apoptosis in M1 macrophages can successfully eliminate the pathogen while in the M2 phenotype it promotes bacterial survival. AMs are permissive to the survival, growth and eventual dissemination of M.tb. There is however a lack in understanding the role of ERS in AMs infected with TB and the impact of infection and ERS on their metabolic profile. The aim of this study was to determine if ERS is established in AMs upon TB infection and its relationship to bacterial survival in AMs. Mouse AMs were infected with M.tb and specimens from different time points post-infection were analyzed for ERS markers and their metabolic profile was determined using LC/MS. We observed a difference in the pattern of ERS and a unique metabolic profile in AMs compared to other macrophages. Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)