Why should cell biologists study microbial pathogens?

Welch, Matthew D.

Studying the cell biology of pathogenesis is contributing to both of these therapeutic avenues. An interesting example involves an emerging connection between autophagy and vaccine efficacy. The bacillus Calmette-Guerin (BCG) vaccine, used to combat tuberculosis caused by the intracellular pathogen Mycobacterium tuberculosis, consists of an attenuated strain of the related bacterium Mycobacterium bovis. BCG has a protective effect against meningitis and disseminated tuberculosis in children but does not prevent primary infection with M. tuberculosis or reactivation of pulmonary infection, which is the main route of spread of the disease. Thus a more effective vaccine is needed. Interestingly, augmenting autophagy with rapamycin was found to enhance presentation of a BCG antigen by antigenpresenting cells and enhance protection against M. tuberculosis infection in animal model (Jagannath et al., 2009) . A similar phenomenon was observed for the yellow fever vaccine YF-17D, a live attenuated virus that, in contrast with BCG, is almost always effective in protecting against infection with the yellow fever virus. It was shown that YF-17D stimulated expression of the kinase GCN2, which in turn stimulated dendritic cells to initiate autophagy and enhanced antigen presentation to T-cells (Ravindran et al., 2014) . These findings suggest that stimulating autophagy may be a general strategy for enhancing antigen presentation and vaccine efficacy.