Mechanistic investigation of immunosuppression in patients with condyloma acuminata

• Published in: Molecular medicine reports Vol. 8; no. 2; pp. 480 - 486
• Main Authors: SHI, YU-JIE, YANG, JIAN, YANG, WENLIN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.08.2013; Spandidos Publications UK Ltd
• Subjects: Adult; Antigens; Cell activation; Cell death; Condyloma acuminatum; Condylomata Acuminata - genetics; Condylomata Acuminata - immunology; Condylomata Acuminata - metabolism; Cytokines; Cytokines - biosynthesis; Cytotoxicity; Enzyme-linked immunosorbent assay; Family medical history; Female; Forkhead protein; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Expression; Glucocorticoids; Growth factors; Hospitals; Human papillomavirus; Humans; Immune system; Immune Tolerance - genetics; Immunoregulation; Immunosuppression; Infections; Interleukin 10; Interleukin 12; Interleukin 2; Interleukin 4; Interleukin 6; Lymphocytes; Lymphocytes T; Male; Middle Aged; MyD88; MyD88 protein; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Natural Cytotoxicity Triggering Receptor 1 - genetics; Natural Cytotoxicity Triggering Receptor 1 - metabolism; Natural killer cells; NK Cell Lectin-Like Receptor Subfamily K - genetics; NK Cell Lectin-Like Receptor Subfamily K - metabolism; NKG2 antigen; Peripheral blood; Polymerase chain reaction; Proteins; Signal transduction; Studies; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism; toll-like receptor; Toll-like receptors; Toll-Like Receptors - genetics; Toll-Like Receptors - metabolism; Transforming growth factor-b; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Viral infections; Young Adult; γ-Interferon
• DOI: 10.3892/mmr.2013.1511
• ISSN: 1791-2997; 1791-3004

Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papillomavirus (HPV) infection. Previous studies have identified that the occurrence, relapse and cancerization of CA is relevant to immune imbalance caused by immune hypofunction or immunoregulatory dysfunction. However, to date, the specific mechanisms accounting for immune imbalance in CA patients have remained elusive. In the present study, changes in the expression levels of myeloid differentiation factor 88 (MyD88) and toll-like receptors (TLRs) were determined in lesion tissues and peripheral blood samples obtained from CA patients by fluorescence quantitative PCR and western blot analysis. The results indicated that TLRs and MyD88 expression was upregulated in the lesion tissues only. In addition, the expression of forkhead box P3, a characteristic marker of regulatory T cells (Tregs), transforming growth factor-β1 and interleukin (IL)-10, inhibitory factors secreted by Tregs and inhibitory costimulatory molecules, cytotoxic T-lymphocyte antigen 4, glucocorticoid-induced TNFR-related protein and programmed cell death protein 1 was observed to be upregulated, indicating that immunosuppression of Tregs was enhanced significantly. However, the expression levels of NKG2D and NKp46, natural killer (NK) cell activation receptors located on the surface of NK cells, decreased markedly indicating that HPV infection inhibits the activation of NK cells. The secretion levels of various cytokines in the peripheral blood of CA patients were detected by enzyme-linked immunosorbent assay revealing that IL-2, IL-12 and interferon-γ levels were markedly lower than that of healthy subjects. By contrast, the expression levels of tumor necrosis factor-α, IL-4 and IL-10 were markedly increased in CA samples compared with the control, with the exception of IL-6. Taken together, these results are consistent with the hypothesis of immunosuppression in CA patients. Increased expression of MyD88 and TLRs is likely to enhance immunosuppression of Tregs, leading to the imbalance of Th1/Th2, cytotoxic T cell type 1 (Tc1)/Tc2 cells and secreted cytokines.