Recognition of Candida albicans by gingival fibroblasts: The role of TLR2, TLR4/CD14, and MyD88

Abstract

Recent evidence indicates that nonprofessional immune cells such as epithelial cells, endothelial cells, and fibroblasts also contribute to innate immunity via secretion of cytokines. Fibroblasts are the principal type of cell found in the periodontal connective tissues and they are involved in the immune response during periodontal disease. The role of fibroblasts in the recognition of pathogens via Toll-like receptors (TLRs) has been established; however, few studies have been conducted concerning the involvement of innate immune receptors in the recognition of Candida albicans by gingival fibroblast. In the current study, we investigate the functional activity of TLR2, cluster of differentiation 14 (CD14), and myeloid differentiation primary response gene 88 (MyD88) molecules in the recognition of C. albicans by gingival fibroblast. First, we identified that gingival fibroblasts expressed TLR2, TLR3, and TLR4. Our results showed that TLR agonists had no effect on these receptors’ expression by TLR2, MyD88, and CD14-deficient cells. Notably, C. albicans and a synthetic triacylated lipoprotein (Pam3CSK4) induced a remarkable increase of TLR3 expression on MyD88-deficient gingival fibroblasts. TLR4 expression levels were lower than TLR2 and TLR3 levels and remained unchanged after TLR agonist stimulation. Gingival fibroblasts presented morphological similarities; however, TLR2 deficiency on these cells leads to a lower proliferative response, whereas the deficiency on CD14 expression resulted in lower levels of type I collagen by these cells. In addition, the recognition of C. albicans by gingival fibroblasts had an effect on the secretion of cytokines and it was dependent on a specific recognition molecule. Specifically, tumor necrosis factor-α (TNF-α ) production after the recognition of C. albicans was dependent on MyD88, CD14, and TLR2 molecules, whereas the production of interleukin-1β (IL-1β ) and IL-13 was dependent on TLR2. These findings are the first to describe a role of gingival fibroblast in the recognition of C. albicans and the pathways involved in this process. An understanding of these pathways may lead to alternative treatments for patients with periodontal disease.

Candida albicans Shields the Periodontal Killer Porphyromonas gingivalis from Recognition by the Host Immune System and Supports the Bacterial Infection of Gingival Tissue

“…Similar to immune cells, fibroblasts use specific sensory receptors to recognize different microorganisms and their surface-exposed molecules (pathogen-associated molecular patterns, PAMPs). Among these factors, the evidence to date has revealed the constitutive expression of selected Toll-like receptors such as TLR2, TLR3, and TLR4 as well as the adhesion molecules ICAM-1 (CD54) and CD44 [62] which are responsible for C. albicans cell recognition [63,64]. The differences in fungal virulence factor sensing by HD and PP fibroblasts, as reflected by the varying cytokine production by both types of host cells, resulted in a significantly lower response of the PP fibroblasts.…”

Innate immune response of human epidermal keratinocytes and dermal fibroblasts to in vitro incubation of Trichophyton benhamiae DSM 6916

“…Moreover, fibroblasts participate actively in establishing the skin's immune response during infectious conditions . It is assumed that fibroblasts act as sentinels producing TLRs , AMPs, pro‐inflammatory cytokines and growth factors – all important mediators of the innate immune response against invading pathogens.…”

Recognition of Candida albicans and Role of Innate Type 17 Immunity in Oral Candidiasis

“…Outer mannoproteins are cross-linked to the inner β-1,6-glucans through a glycosylphosphatidylinositol (GPI) remnant [ 37 ]. Altogether ß-glucans, mannans as well as nucleic acids of C. albicans , form a group of so-called pathogen- associated molecular patterns (PAMPs) [ 38 , 39 ]. Identification of nonself molecules via PAMPs can occur by pattern-recognition receptors (PRRs) in both epithelial and myeloid cells.…”