My research interest has long been innate immunity, with a focus on understanding host responses to mycobacteria and viruses and virulence strategies employed by these pathogens to parasitize host cells. My early work on TLRs is highly cited and helped clarify aspects of ligand recognition by TLRs, also because I made the first monoclonal Ab against human TLR2. As a young researcher, I made the ground-breaking discovery of a novel iron-withholding host defense strategy (Flo et al., Nature 2004), and since then I have been intrigued by how pathogens like mycobacteria and HIV can survive within humans for a lifetime. We recently reported the controversial finding that HIV is detected by TLR8 in T cells and showed that TLR8 ligands are potentially promising for new HIV therapy (a). My approach to spatiotemporally dissecting host-pathogen interactions using microscopy combined with molecular techniques has led to discoveries on pathogen recognition, inflammatory signaling, and cell death. We have used different microscopy methods including time-lapse and correlative light- and 3D electron microscopy (CLEM) for determining how mycobacteria are sensed as they move within immune cells (b-c). Using CLEM, we were the first to image inflammasomes in situ in M. tuberculosis-infected macrophages. Our most recent work reveals that glycine's long-known cytoprotective activity is due to glycine targeting of NINJ1, a newly identified executioner of plasma membrane rupture (d).