Abstract

Our prevailing view of vertebrate host defense is strongly shaped by the notion of a specialized set of immune cells as sole guardians of antimicrobial resistance. Yet this view greatly underestimates a capacity for most cell lineages – the majority of which fall outside the traditional province of the immune system – to defend themselves against infection. This ancient and ubiquitous form of host protection is termed cell-autonomous immunity and operates across all three domains of life. I will discuss the organizing principles that govern cellular self-defense and how intracellular compartmentalization has shaped its activities to provide effective protection against a wide variety of microbial pathogens. As an instructive example of cell-autonomous immunity I will illustrate how cells deploy autophagy to protect their cytosol from bacterial invasion. Invading bacteria must be specifically recognized to ensure their efficient delivery into autophagosomes. Emphasis will be given to how ‘eat-me’ signals become associated with cytosol-invading bacteria, how cargo-selecting autophagy receptor target cytosolic bacteria for destruction, and how professional cytosol-dwelling bacteria escape from autophagy.