Gram-positive anaerobic cocci guard skin homeostasis by regulating host-defense mechanisms

Danique A van der Krieken; Gijs Rikken; Thomas H A Ederveen; Patrick A M Jansen; Diana Rodijk-Olthuis; Luca D Meesters; Ivonne M J J van Vlijmen-Willems; Bram van Cranenbroek; Renate G van der Molen; Joost Schalkwijk; Ellen H van den Bogaard; Patrick L J M Zeeuwen

doi:10.1016/j.isci.2023.106483

Gram-positive anaerobic cocci guard skin homeostasis by regulating host-defense mechanisms

iScience. 2023 Mar 23;26(4):106483. doi: 10.1016/j.isci.2023.106483. eCollection 2023 Apr 21.

Affiliations

¹ Department of Dermatology, Radboud University Medical Center (Radboudumc), 6500HB Nijmegen, the Netherlands.
² Center for Molecular and Biomolecular Informatics (CMBI), Radboudumc, 6500HB Nijmegen, the Netherlands.
³ Laboratory Medicine, Laboratory of Medical Immunology, Radboudumc, 6500HB Nijmegen, the Netherlands.

Abstract

In atopic dermatitis (AD), chronic skin inflammation is associated with skin barrier defects and skin microbiome dysbiosis including a lower abundance of Gram-positive anaerobic cocci (GPACs). We here report that, through secreted soluble factors, GPAC rapidly and directly induced epidermal host-defense molecules in cultured human keratinocytes and indirectly via immune-cell activation and cytokines derived thereof. Host-derived antimicrobial peptides known to limit the growth of Staphylococcus aureus-a skin pathogen involved in AD pathology-were strongly upregulated by GPAC-induced signaling through aryl hydrocarbon receptor (AHR)-independent mechanisms, with a concomitant AHR-dependent induction of epidermal differentiation genes and control of pro-inflammatory gene expression in organotypic human epidermis. By these modes of operandi, GPAC may act as an "alarm signal" and protect the skin from pathogenic colonization and infection in the event of skin barrier disruption. Fostering growth or survival of GPAC may be starting point for microbiome-targeted therapeutics in AD.

Keywords: Dermatology; Microbiology; microbiome.