A Case for Phosphoinositide 3-Kinase–Targeted Therapy for Infectious Disease

PI3Ks activate critical signaling cascades and have multifaceted regulatory functions in the immune system. Loss-of-function and gain-of-function mutations in the PI3Kδ isoform have revealed that this enzyme can substantially impact immune responses to infectious agents and their products. Moreover, reports garnered from decades of infectious disease studies indicate that pharmacologic inhibition of the PI3K pathway could potentially be effective in limiting the growth of certain microbes via modulation of the immune system. In this review, we briefly highlight the development and applications of PI3K inhibitors and summarize data supporting the concept that PI3Kδ inhibitors initially developed for oncology have immune regulatory potential that could be exploited to improve the control of some infectious diseases. This repurposing of existing kinase inhibitors could lay the foundation for alternative infectious disease therapy using available therapeutic agents.