Bidirectional Communication Between the Innate and Adaptive Immune Systems

Effective bidirectional communication between the innate and adaptive immune systems is crucial for tissue homeostasis and protective immunity against infections. The innate immune system is responsible for the early sensing of and initial response to threats, including microbial ligands, toxins, and tissue damage. Pathogen-related information, detected primarily by the innate immune system via dendritic cells, is relayed to adaptive immune cells, leading to the priming and differentiation of naive T cells into effector and memory lineages. Memory T cells that persist long after pathogen clearance are integral for durable protective immunity. In addition to rapidly responding to reinfections, memory T cells also directly instruct the interacting myeloid cells to induce innate inflammation, which resembles microbial inflammation. As such, memory T cells act as newly emerging activators of the innate immune system and function independently of direct microbial recognition. While T cell–mediated activation of the innate immune system likely evolved as a protective mechanism to combat reinfections by virulent pathogens, the detrimental outcomes of this mechanism manifest in the forms of autoimmunity and other T cell–driven pathologies. Here, we review the complexities and layers of regulation at the interface between the innate and adaptive immune systems to highlight the implications of adaptive instruction of innate immunity in health and disease.