Head and neck dermatitis is exacerbated by Malassezia furfur colonization, skin barrier disruption, and immune dysregulation

Front Immunol. 2023 Feb 22:14:1114321. doi: 10.3389/fimmu.2023.1114321. eCollection 2023.

Abstract

Introduction & objectives: Head and neck dermatitis (HND) is a refractory phenotype of atopic dermatitis (AD) and can be a therapeutic challenge due to lack of responsiveness to conventional treatments. Previous studies have suggested that the microbiome and fungiome may play a role in inducing HND, but the underlying pathogenic mechanisms remain unknown. This study aimed to determine the link between HND and fungiome and to examine the contribution of Malassezia furfur.

Materials and methods: To identify the effect of the sensitization status of M. furfur on HND, 312 patients diagnosed with AD were enrolled. To elucidate the mechanism underlying the effects of M. furfur, human keratinocytes and dermal endothelial cells were cultured with M. furfur and treated with Th2 cytokines. The downstream effects of various cytokines, including inflammation and angiogenesis, were investigated by real-time quantitative PCR. To identify the association between changes in lipid composition and M. furfur sensitization status, D-squame tape stripping was performed. Lipid composition was evaluated by focusing on ceramide species using liquid chromatography coupled with tandem mass spectrometry.

Results: Increased sensitization to M. furfur was observed in patients with HND. Additionally, sensitization to M. furfur was associated with increased disease severity in these patients. IL-4 treated human keratinocytes cultured with M. furfur produced significantly more VEGF, VEGFR, IL-31, and IL-33. IL-4/M. furfur co-cultured dermal endothelial cells exhibited significantly elevated VEGFR, TGF-β, TNF-α, and IL-1β levels. Stratum corneum lipid analysis revealed decreased levels of esterified omega-hydroxyacyl-sphingosine, indicating skin barrier dysfunction in HND. Finally, M. furfur growth was inhibited by the addition of these ceramides to culture media, while the growth of other microbiota, including Cutibacterium acnes, were not inhibited.

Conclusions: Under decreased levels of ceramide in AD patients with HND, M. furfur would proliferate, which may enhance pro-inflammatory cytokine levels, angiogenesis, and tissue remodeling. Thus, it plays a central role in the pathogenesis of HND in AD.

Keywords: LC-MS/MS; Malassezia; atopic dermatitis; ceramide; head and neck dermatitis; lipid analysis; red face syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ceramides
  • Cytokines
  • Dermatitis, Atopic*
  • Endothelial Cells
  • Humans
  • Interleukin-4
  • Lipids
  • Malassezia* / physiology

Substances

  • Interleukin-4
  • Cytokines
  • Ceramides
  • Lipids

Grants and funding

This study was supported by the National Research Foundation of Korea grants funded by the Korea government (Ministry of Science and ICT) (No. NRF-2020R1A2C1009916 and NRF-2021R1A4A5032185 [to C.O.P.]), grants of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant HI14C1324 [to C.O.P.] and grant HP20C0018 [to K-H.L.]), and a faculty research grant of Yonsei University College of Medicine (6-2021-0074 [to C.O.P.]).