Activation and pathogenic manipulation of the sensors of the innate immune system

The innate immune system detects the presence of microbes through different families of pattern-recognition receptors (PRRs). PRRs detect pathogens of all origins and trigger signaling events that activate innate and adaptive immunity. These events need to be tightly regulated in order to ensure optimal activation when required, and minimal signaling in the absence of microbial encounters. This regulation is achieved, at least in part, through the precise subcellular positioning of receptors and downstream signaling proteins. Consequently, mislocalization of these proteins inhibits innate immune pathways, and pathogens have evolved to alter host protein localization as a strategy to evade immune detection. This review describes the importance of subcellular localization of various PRR families and their adaptors, and highlights pathogenic immune evasion strategies that operate by altering immune protein localization.