New Immunological Markers in Chromoblastomycosis—The Importance of PD-1 and PD-L1 Molecules in Human Infection

Author:

Cavallone Italo N.12ORCID,Belda Walter3,de Carvalho Caroline Heleno C.3ORCID,Laurenti Marcia D.3ORCID,Passero Luiz Felipe D.14ORCID

Affiliation:

1. Institute of Biosciences, São Paulo State University (UNESP), Praça Infante Dom Henrique, s/n, São Vicente 11330-900, Brazil

2. Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, São Paulo University, São Paulo 01246-903, Brazil

3. Dermatology Department, Medical School, São Paulo University, Clinics Hospital, São Paulo 05403-000, Brazil

4. Institute for Advanced Studies of Ocean (IEAMAR), São Paulo State University (UNESP), Rua João Francisco Bensdorp, 1178, São Vicente 11350-011, Brazil

Abstract

The pathogenesis of chromoblastomycosis (CBM) is associated with Th2 and/or T regulatory immune responses, while resistance is associated with a Th1 response. However, even in the presence of IFN-γ, fungi persist in the lesions, and the reason for this persistence is unknown. To clarify the factors associated with pathogenesis, this study aimed to determine the polarization of the cellular immune response and the densities of cells that express markers of exhaustion in the skin of CBM patients. In the skin of patients with CBM, a moderate inflammatory infiltrate was observed, characterized primarily by the occurrence of histiocytes. Analysis of fungal density allowed us to divide patients into groups that exhibited low and high fungal densities; however, the intensity of the inflammatory response was not related to mycotic loads. Furthermore, patients with CBM exhibited a significant increase in the number of CD4+ and CD8+ cells associated with a high density of IL-10-, IL-17-, and IFN-γ-producing cells, indicating the presence of a chronic and mixed cellular immune response, which was also independent of fungal load. A significant increase in the number of PD-1+ and PD-L1+ cells was observed, which may be associated with the maintenance of the fungus in the skin and the progression of the disease.

Funder

São Paulo Research Foundation

LIM50-FMUSP

PROPe-UNESP

FAPESP

National Council for Scientific and Technological Development

Publisher

MDPI AG

Subject

Plant Science,Ecology, Evolution, Behavior and Systematics,Microbiology (medical)

Reference87 articles.

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