IFN-inducible GTPases and immunity to intracellular pathogens

By eliciting host antimicrobial programs in nearly all nucleated cells interferons (IFNs) help orchestrate the innate immune response of mammals to a diverse array of microbial pathogens. Recent work has highlighted the complexity of this transcriptional repertoire and the emergence of several families of IFN-inducible guanosine 5′ triphosphatases (GTPases) – p47, guanylate-binding protein (GBP), Mx and very large inducible GTPases (VLIG) – that subsume pathogen-specific roles. Such specificity arises from a combination of both the type and timing of inductive stimuli, target-cell population, subcellular binding partners and the infectious agent encountered. Evolution of different GTPase families to combat compartmentalized versus cytosolic pathogens reveals a hitherto unexpected level of intracellular discrimination during vertebrate host defense. By eliciting host antimicrobial programs in nearly all nucleated cells interferons (IFNs) help orchestrate the innate immune response of mammals to a diverse array of microbial pathogens. Recent work has highlighted the complexity of this transcriptional repertoire and the emergence of several families of IFN-inducible guanosine 5′ triphosphatases (GTPases) – p47, guanylate-binding protein (GBP), Mx and very large inducible GTPases (VLIG) – that subsume pathogen-specific roles. Such specificity arises from a combination of both the type and timing of inductive stimuli, target-cell population, subcellular binding partners and the infectious agent encountered. Evolution of different GTPase families to combat compartmentalized versus cytosolic pathogens reveals a hitherto unexpected level of intracellular discrimination during vertebrate host defense.