Effector Pathways of Toll-like Receptor-inducible Innate Immune Responses in Macrophages

ABSTRACT

Toll-like receptors (TLR) are well-characterized pattern recognition receptors that can recognize and respond to diverse pathogen-associated or danger-associated molecular patterns during infection. TLR signaling in macrophages triggers in the intracellular signaling pathways through the recruitment of various adaptor and signaling proteins, and results in the activation of effector mechanisms and pathways that are important for host defense to intracellular bacteria. Effector mechanisms include inflammatory responses, cytokine generation, production of reactive oxygen species, and antimicrobial proteins. Accumulating studies showed that autophagy is a key pathway in the maintenance of homeostasis and housekeeping functions during infection and inflammation. In this review, we summarize the major effector pathways and mechanisms in the activation of TLR-inducible innate immune responses in macrophages. In addition, we focus the emerging evidence of crosstalk between autophagy and TLR-mediated signaling in terms of effector function of innate immune responses. A better understanding of effector functions by the activation of TLR-mediated signaling cascades contributes to the development of new therapeutics and vaccines against various intracellular pathogenic infections.