Photodynamic Therapy for Genital Warts Causes Activation of Local Immunity

J Cutan Med Surg. 2019 Jul/Aug;23(4):370-379. doi: 10.1177/1203475419838548. Epub 2019 Apr 22.

Abstract

Background: 5-aminolevulinic acid photodynamic therapy (PDT) for genital warts is effective, safe, and can prevent recurrence. It is believed that PDT can induce immune responses, but the mechanism is not completely understood.

Objectives: The objectives of this article are to confirm the effect of PDT for genital warts on local immunity and to investigate the recruitment and significance of immune cells in tissues.

Methods: Local immune changes in T lymphocytes (CD3+, CD4+, CD8+), plasmacytoid dendritic cells (pDCs) (CD123+), and myeloid dendritic cells (CD1a+) after PDT in patients were evaluated by immunohistochemistry staining. Changes in mRNA levels of IFN-γ, IFN-α, IFN-ß, interferon-stimulated gene 15 kDa (ISG-15), Mx2, Toll-like receptor 9 (TLR9), and interferon regulatory factor 7 (IRF7) were analyzed by real-time quantitative polymerase chain reaction.

Results: At 4 hours after PDT, CD4+ increased, accompanied by increased levels of mRNA expression of IFN-γ, but CD4+ and mRNA expression levels of IFN-γ were decreased at 24 hours after PDT. CD123+ pDCs showed an increasing trend. CD1a+ LCs in the epidermis gradually decreased, and DCs in the epidermis gradually increased. CD3+ infiltrated and migrated to the superficial dermis, but CD8+ did not change significantly after PDT. The mRNA expression levels of IFN-α, IFN-ß, ISG-15, Mx2, TLR9, and IRF7 showed an increasing trend after PDT. As compared with the patients without significantly increased IFN-α and IFN-ß after PDT sessions, patients with significant increases needed fewer sessions of PDT for remission.

Conclusions: PDT for genital warts can activate T lymphocyte-mediated, DC-related, and pDC-related immunity. The clinical efficacy of PDT for genital warts may be related to the increased levels of IFN-α and IFN-ß after treatment.

Keywords: HPV; PDT; Toll-like receptors; genital warts; myeloid dendritic cells; plasmacytoid dendritic cells.

MeSH terms

  • Adult
  • Aminolevulinic Acid / pharmacology*
  • Aminolevulinic Acid / therapeutic use
  • Antigens, CD1 / metabolism
  • CD3 Complex / metabolism
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology
  • Condylomata Acuminata / drug therapy*
  • Cytokines / genetics
  • Epidermis / immunology*
  • Epidermis / metabolism
  • Female
  • Gene Expression / drug effects
  • Humans
  • Interferon Regulatory Factor-7 / genetics
  • Interferon-alpha / genetics
  • Interferon-beta / genetics
  • Interferon-gamma / genetics
  • Interleukin-3 Receptor alpha Subunit / metabolism
  • Langerhans Cells / drug effects
  • Langerhans Cells / immunology*
  • Langerhans Cells / metabolism
  • Male
  • Middle Aged
  • Myxovirus Resistance Proteins / genetics
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology*
  • Photosensitizing Agents / therapeutic use
  • RNA, Messenger / metabolism
  • Toll-Like Receptor 9 / genetics
  • Ubiquitins / genetics
  • Young Adult

Substances

  • Antigens, CD1
  • CD1a antigen
  • CD3 Complex
  • Cytokines
  • IL3RA protein, human
  • IRF7 protein, human
  • Interferon Regulatory Factor-7
  • Interferon-alpha
  • Interleukin-3 Receptor alpha Subunit
  • MX2 protein, human
  • Myxovirus Resistance Proteins
  • Photosensitizing Agents
  • RNA, Messenger
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Ubiquitins
  • ISG15 protein, human
  • Interferon-beta
  • Interferon-gamma
  • Aminolevulinic Acid