Impact of the interaction of indoles produced by Malassezia spp. with the macrophage aryl hydrocarbon receptor in the immune response of patients with pityriasis versicolor

• Grant number: 24/05761-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2025
• End date: March 31, 2028
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Maria da Gloria Sousa Stafocker
• Grantee: Giovanna Azevedo Celestrino
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The skin harbors a wide variety of microbial populations, which together with theirstructural elements, metabolites and produced molecules, compose the microbiome. Thegenus Malassezia represents around 80% of cutaneous fungal species, being the mostprevalent fungal commensal. Although it is a commensal, Malassezia has been associatedwith some skin diseases such as pityriasis versicolor, a superficial fungal infection,characterized by excessive fungal growth on the skin, and is generally asymptomatic. Onebiochemical process of particular interest in this yeast is production of indole derivativeswhen tryptophan is the single nitrogen source. These indoles have been shown to bepotent ligands of the aryl hydrocarbon receptor (AhR), a cytosolic transcription factor,which is activated upon binding with different ligands. The effects of AhR signaling aremostly related to inflammatory skin diseases, but also participate in homeostasis andmodulation of the immune response. Until now, work evaluating the role of Malasseziaindoles has been limited to the effect of some of these metabolites in isolated cells, whilethe mechanism that involves the recognition and mediation of the immune response afterinteraction with the AhR and which pathways this receptor uses, remains unexplained.So, we propose to evaluate the response of macrophages from patients with pityriasisversicolor after interaction with indoles derived from Malassezia, the participation of AhRin the recognition of this fungus and identify the pattern of the immune response. Theunderstanding of these pathways may contribute to better management of this pathogen.