Abstract
Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for pathogen recognition and induction of innate immune responses. Since their discovery, TLRs have revolutionized the field of immunology by filling the gap between the initial recognition of pathogens by innate immune cells and the activation of the adaptive immune response. TLRs critically link innate immunity to adaptive immunity by regulating the activation of antigen-presenting cells and key cytokines. Furthermore, recent studies also have shown that TLR signaling can directly regulate the T cell activation, growth, differentiation, development, and function under diverse physiological conditions. This review provides an overview of TLR signaling pathways and their regulators and discusses how TLR signaling, directly and indirectly, regulates cell-mediated immunity. In addition, we also discuss how TLR signaling is critically important in the host’s defense against infectious diseases, autoimmune diseases, and cancer.
Highlights
The innate immune system is the first line of defense against infectious pathogens and cancer by sensing and responding to the structure-conserved molecules of the pathogens as well as the endogenous ligands released from damaged cells
Besides different subsets of cluster of differentiation 4 (CD4)+ Treg cells, we found that the cluster of differentiation 8 (CD8)+ Treg cells and gd-TCR Treg cells in prostate and breast cancer express a low level of human TLR8 molecules [158, 159]
This review provides an updated overview of Toll-like receptors (TLRs) signaling and its critical role in cell-mediated immunity
Summary
The innate immune system is the first line of defense against infectious pathogens and cancer by sensing and responding to the structure-conserved molecules of the pathogens (pathogenassociated molecular patterns, or PAMPs) as well as the endogenous ligands released from damaged cells (damage-associated molecular patterns, or DAMPs). The mammalian homolog of the Toll receptor ( termed TLR4) was first discovered in 1997 to play a critical role the in innate immunity by inducing the expression of inflammatory responses-related genes [10]. These findings revolutionized our understanding of the immune system and triggered an explosion of research in PRRs. To date, 10 TLRs have been identified in humans (TLR1–TLR10) and 12 in mice (TLR1–TLR9 and TLR11–TLR13). The production of cytokines, expression of costimulatory molecules, and antigen-presenting activity in APCs are induced or enhanced by microbe-derived adjuvants, which are recognized by TLRs expressed on APCs and boost the APC signaling to promote activation of immune responses in T cells [21]. This review article mainly summarizes the recent progress on TLR signaling pathways and their crucial role in cell-mediated immunity
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