Toll-like receptors in skin infections and inflammatory diseases - PubMed (original) (raw)

Review

Toll-like receptors in skin infections and inflammatory diseases

Yuping Lai et al. Infect Disord Drug Targets. 2008 Sep.

Abstract

The skin is the ultimate example of the function of innate immunity, it alerts the host of danger by many systems including sensing pathogen-associated molecule patterns (PAMPs) through Toll-like receptors and other pattern recognition receptors (PRRs), yet normally provides defense without inflammation. The skin responds rapidly to invading microbes by producing antimicrobial peptides or other antimicrobial intermediates before cytokine release results in inflammation. To achieve maximal immune responses for clearing invading microbes, the activation of select PRRs in skin then initiates and shapes adaptive immune responses through the activation of dendritic cells and recruitment of T cell subsets. Importantly, cross-talk between TLRs can influence this system in several ways including augmenting or suppressing the immune response. As a consequence of their pivotal role, TLR responses need to be tightly controlled by associated negative regulators or negative feedback loops to prevent detrimental effects from TLRs overactivation. This review focuses on describing the involvement of TLRs in the development of skin infections and inflammatory diseases, and highlights the potential application of TLR agonists or antagonists in these skin diseases.

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Figures

Fig 1

Fig 1. TLR signaling

Upon the stimulation by cognate ligands, all TLRs, except for TLR3, recruit MyD88, IRAKs and TRAF6 to activate TLR signaling. Subsequently, TLR signaling diverges at TRAF6 to two different pathways to produce inflammatory cytokines. However, TLR3 utilizes TRIF for the activation of the TRIF-dependent pathway to produce type I interferons and inflammatory cytokines.

Fig 2

Fig 2. The immunomodulatory effects of TLR activation

The activation of TLRs is double-edge sword. In addition to promoting NK activity and phagocytosis, appropriated TLR stimulation also boosts the host to produce inflammatory cytokines, chemokines, antimicrobial peptides and other intermediates against infectious diseases in skin. Moreover, the activation of TLRs can initiate and shape an adaptive immune response to co-administered vaccine as vaccine adjuvant. However, excessive TLR stimulation may lead to some inflammatory diseases, sepsis or autoimmune diseases in the skin.

Fig 3

Fig 3. Negative regulators for TLR signaling

TLR signaling is negatively regulated by several negative regulators (Shown in Red). Both MyD88s and IRAK-M suppress the downstream signaling of MyD88. TRAF1 turns off TRIF signaling. TRAF4 and A20 bind and block TRAF6. SIGIRR expresses in epithelial cells and antagonize TLR4 signaling. ST2L inhibits both TLR2 and TLR4 signaling.

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