As an infectious diseases physician-scientist, my research is motivated by the mysteries I encounter in my medical practice. One such conundrum is how the same infection can cause highly variable outcomes in different patients. One of the factors that determines infection severity is the “context” in which the immune system is operating. This context can include age, sex, chronic diseases, and importantly, also the recent exposure history of an immune cell. When innate immune cells such as macrophages are exposed to cytokines and pathogen-associated molecules their signaling networks and epigenetic states get re-wired. This reprogramming affects their response to a subsequent infection and may also lead to post-infectious immune dysfunction. My research examines the molecular mechanisms of macrophage reprogramming and how this relates to the variable outcomes of human infections.