Monocyte-Derived Dendritic Cells Can Revert In Vitro Antigen-Specific Cellular Anergy in Active Human Paracoccidioidomycosis

Author(s)

Sato, Paula Keiko ^{[1, 2, 3]} ; Oshiro, Telma Miyuki ^{[1, 4]} ; Passos, Erika Cano ^{[2, 3]} ; Miranda, Tatiana Giselle Rodrigues ^{[1, 2]} ; Diogo, Constancia Lima ^{[2, 3]} ; Fonseca, Claudia de Abreu ^{[2, 3]} ; Sadahiro, Aya ^{[1, 5]} ; de Almeida, Sandro Rogerio ^[6] ; Shikanai-Yasuda, Maria Aparecida ^{[1, 2, 3]}

Affiliation

^[1] Univ Sao Paulo, Fac Med FMUSP, Dept Infect Dis, BR-05403000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Lab Med Invest Immunol LIM 48, BR-05403000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med FMUSP, Inst Trop Med, BR-05403000 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Med Invest Dermatol & Immunodeficiencies LIM, BR-05403000 Sao Paulo - Brazil

^[5] Univ Fed Amazonas, Inst Ciencias Biol, Dept Parasitol, BR-69080 Manaus, Amazonas - Brazil

^[6] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508000 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF FUNGI; v. 7, n. 3 MAR 2021.
• Web of Science Citations: 0

Abstract

We investigated the in vitro effects of two Paracoccidioides brasiliensis antigens on monocyte-derived dendritic cells (moDCs) from patients with paracoccidioidomycosis (PCM). MoDCs from patients with active or treated PCM and non-PCM subjects were generated, stimulated with TNF-alpha, and P. brasiliensis antigens, 43 kDa glycoprotein (gp43) and cell-free antigen (CFA), and analyzed by flow cytometry and enzyme-linked immunosorbent assays (ELISA). Our data revealed that patients with PCM had a high frequency of HLA-DR+ cells, but the treated group had more CD86(+) cells with increased IL-12p40. Patients with active PCM had more CD80(+) moDCs, and as a novel finding, large amounts of chemokine (C-C motif) ligand 18 (CCL18) in the supernatants from their in vitro moDC cultures. Both gp43- and CFA-stimulated moDCs from the patients with PCM successfully reverted the in vitro antigen-specific anergy, inducing a proliferative response. However, CFA-stimulated moDCs led to higher lymphoproliferation, with increased IFN-gamma and TNF-alpha in the cells from the patients with active PCM compared with gp43. These original results combined with constant IL-10 and increased IL-12p40 levels suggest that a more complex antigen, such as CFA, may be a better inducer of the protective Th1 immune response than purified gp43 is, and a suitable target for future studies on anti-P. brasiliensis dendritic cell (DC)-based vaccines. (AU)