Altered distribution of peripheral blood dendritic cell subsets in patients with pulmonary paracoccidioidomycosis

• Published in: Acta tropica Vol. 173; pp. 185 - 190
• Main Authors: Venturini, James, Cavalcante, Ricardo Souza, Moris, Daniela Vanessa, Golim, Márjorie de Assis, Levorato, Adriele Dandara, Reis, Karoline Hagatha dos, Arruda, Maria Sueli Parreira de, Mendes, Rinaldo Poncio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2017
• Subjects: Adult; Antifungal Agents - therapeutic use; Antifungal treatment; Case-Control Studies; Cytokines - genetics; Cytokines - metabolism; Dendritic Cells - physiology; Emphysema; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Regulation - immunology; Humans; Latin America; Lung - cytology; Lung - pathology; Male; Middle Aged; Myeloid dendritic cells; Paracoccidioides; Paracoccidioidomycosis - drug therapy; Paracoccidioidomycosis - immunology; Paracoccidioidomycosis - pathology; Plasmacytoid dendritic cells; Pulmonary fibrosis; Young Adult; Plasmacytoid dendritic cells; Pulmonary fibrosis; Antifungal treatment; Emphysema; Paracoccidioides; Myeloid dendritic cells
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2017.06.007

•Paracoccidioidomycosis (PCM) is a systemic fungal disease endemic in Latin America.•Patients usually develop pulmonary sequelae, causing breathing difficulties.•Few studies have addressed the influence of sequelae in the immune response.•Dendritic cells (DC) are important for polarization of the adaptive immune response.•Distribution of myeloid and plasmocytoid DCs is altered in PCM, even after treatment.
Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi from the genus Paracoccidioides in Latin America. PCM-patients (PCM-p) are classified as having acute/subacute or chronic (CF) clinical forms. CF is responsible for 75%–90% of all cases, affects mainly adults over 30 years old and the clinical manifestation are associated mainly with lungs and mucosa of upper airdigestive tract. In addition, the CF patients exhibit fibrosis of the lungs, oral mucous membranes and adrenals, and pulmonary emphysema. Consequently, CF PCM-p with active disease, as well as those that have been apparently cured, seem to be an interesting model for studies aiming to understand the long-term host-fungi relationship and hypoxia. Dendritic cells (DCs) constitute a system that serve as a major link between innate and adaptive immunity composed of several subpopulations of cells including two main subsets: myeloid (mDCs) and plasmacytoid (pDCs). The present study aimed to access the distribution of PBDC subsets of CF PCM-p who were not treated (NT) or treated (apparently cured – AC). CF PCM-p were categorized into two groups, consisting of 9 NTs and 9 ACs. Twenty-one healthy individuals were used as the control group. The determination of the PBDC subsets was performed by FACS (fluorescence-activated cell sorting) and the dosage of serum TNF-α, IL1β, IL-18, CCL3, IL-10 and basic fibroblast growth factor (bFGF) by ELISA (enzyme-linked immunosorbent assay). A high count and percentage of mDCs was observed before treatment, along with a low count of pDCs in treated patients. Furthermore, the mDC:pDC ratio and serum levels of TNF-α was higher in both of the PCM-p groups than in the control group. In conclusion, our findings demonstrated that active PCM influences the distribution of mDCs and pDCs, and after treatment, PCM-p retained a lower count of pDCs associated with pro-inflammatory profile. Therefore, we identified new evidences of persistent immunological abnormalities in PCM-p after treatment. Even these patients showing fungal clearance after successful antifungal treatment; the hypoxia, triggered by the persistent pulmonary sequelae, possibly continues to interfere in the immune response.