Review of the Innate Immune Response in Acne vulgaris: Activation of Toll-Like Receptor 2 in Acne Triggers Inflammatory Cytokine Responses

Abstract

Acne vulgaris is a common disorder that affects 40–50 million people in the USA alone. The pathogenesis of acne is multifactorial, including hormonal, microbiological and immunological mechanisms. One of the factors that contributes to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular mechanism by which P. acnes induces inflammation is not known. Recent studies have demonstrated that microbial agents trigger cytokine responses via Toll-like receptors (TLRs). TLRs are pattern recognition receptors that recognize pathogen-associated molecular patterns conserved among microorganisms and elicit immune responses. We investigated whether TLR2 mediates P. acnes-induced cytokine production in acne. Using transfectant cells we found that TLR2 was sufficient for NF-ĸB activation in response to P. acnes. In addition, peritoneal macrophages from wild-type, TLR6 knockout and TLR1 knockout mice, but not TLR2 knockout mice, produced IL-6 in response to P. acnes.P. acnes induced activation of IL-12 and IL-8 production by primary human monocytes, and this cytokine production was inhibited by anti-TLR2-blocking antibody. Finally, in acne lesions, TLR2 was expressed on the cell surface of macrophages surrounding pilosebaceous follicles. These data suggest that P. acnes triggers inflammatory cytokine responses in acne by activation of TLR2. As such, TLR2 may provide a novel target for the treatment of this common skin disease.

An update on the role of the sebaceous gland in the pathogenesis of acne

“…Both cell types can be activated by P. acnes via toll-like receptors (TLR), CD14 and CD1 molecules. 88 The expression of TLR2, TLR4, TLR6 and CD14 has been already documented in SZ95 sebocytes. 91,92 Recent evidence has indicated that human sebaceous glands may contribute to the skin immune defense by releasing antimicrobial peptides (AMP).…”

“…It is known that P. acnes-induced cytokine production is mediated by Toll-like receptor (TLR) 2. [87][88][89][90] The pilosebaceous unit is an immunocompetent organ. Keratinocytes and sebocytes may act as immune cells capable of pathogen recognition and abnormal lipid presentation.…”

Studying the genetic predisposing factors in the pathogenesis of acne vulgaris

“…The pathogen recognition receptors TLR2 and TLR4 are important in the recognition of P acnes in epidermal keratinocytes, and through the initiation of gene expression changes, they regulate downstream innate immune events [43,44].…”

Soy Isoflavones Reduce Toll-like Receptor-2 Levels in Acne Vulgaris

“…Toll-like receptor-2 is a specific receptor for endotoxins, especially cell wall peptidoglycan, of gram-positive extracellular bacteria, including P. acnes. Number of receptors in the cellular surface is inconsistent, but either up-regulation or down-regulation may occur [4]. Toll-like receptor-2 has in important role in recognizing pathogens presented to the infectious agents, and in mediating the production of cytokine required to develop an effective immunity [5].…”

“…TLR-2 will bind the peptidoglycans in P. acnes cell wall and activate the inflammatory response through the nuclear factor kappa B (NF-κB) pathway, whereas interleukin-8 (IL-8) is known as a central inflammatory mediator. One of the role of IL-8 is a neutrophil chemotactic factor in the pathogenesis of AV [4][5][6][7][8][9].…”