Macrophages and Infection Control

We have developed a zebrafish model for the study of infection focusing on mycobacteria, which are intracellular pathogens of macrophages, inducing their aggregation into hallmark structures called granulomas. Exploiting the optical transparency and genetic tractability of the developing zebrafish, we can visualize macrophage-pathogen interactions in great detail in live animals and study the consequences of genetic perturbations. We have identified pathways through which macrophages restrict infection and also those that alter macrophage migration, microbicidal capacity, susceptibility to apoptosis and necrosis so as to render them as tools for bacterial expansion. The complex interactions we have uncovered provide new insights into macrophage biology that are relevant not only for tuberculosis and other infectious diseases but also for the pathogenesis of noninfectious inflammatory diseases in which macrophages are increasingly recognized to play an integral role.