Host-directed immunotherapy to fight infectious diseases

PURPOSE OF REVIEW: This review provides readers with examples of refractory infections due to inborn errors of immunity, highlighting how they may be successfully treated by deducing and targeting the underlying immunodeficiency. RECENT FINDINGS: The use of host-directed immunotherapy to treat infectious disease in inborn errors of immunity is currently limited but growing. Different strategies include depleting the cellular reservoir for pathogens with restricted cell-tropism; augmenting the diminished effector response; and restoring molecular equipoise. The immunotherapies illustrated are existing drugs that have been re-purposed and rationally used, depending on the molecular or cellular impact of the mutation. As more biologic response modifiers and molecular targeted therapies are developed for other indications, they open the avenues for their use in inborn errors of immunity. Conversely, as more molecular pathways underlying defective immune responses and refractory infections are elucidated, they lend themselves to tractability with these emerging therapies. SUMMARY: Infections that fail appropriate antimicrobial therapy are a harbinger of underlying inborn errors of immunity. Dissecting the mechanism by which the immune system fails provides opportunities to target the host response and make it succeed.