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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02445

New role of P. brasiliensis α-glucan: differentiation of non-conventional dendritic cells

  • 1University of Tennessee Health Science Center (UTHSC), United States
  • 2University of Brasilia, Brazil
  • 3Gonçalo Moniz Institute (IGM), Brazil

The cell wall has a critical role in the host immune response to fungal pathogens. In this study, we investigated the influence of two cell wall fractions of the dimorphic fungi Paracoccidioides brasiliensis (Pb) in the in vitro generation of monocyte-derived dendritic cells (MoDCs). Monocytes were purified from the peripheral blood of healthy donors and cultivated for seven days in medium supplemented with IL-4 and GM-CSF in the presence of Pb cell wall fractions: the alkali-insoluble F1, constituted by β-1,3-glucans, chitin and proteins, and the alkali-soluble F2, mainly constituted by α-glucan. MoDCs phenotypes were evaluated regarding cell surface expression of CD1a, DC-SIGN, HLA-DR, CD80 and CD83 and production of cytokines. The α-glucan-rich cell wall fraction downregulated the differentiation of CD1a+ MoDCs, a dendritic cell subset that stimulate Th1 responses. The presence of both cell fractions inhibited DC-SIGN and HLA-DR expression, while the expression of maturation markers was differentially induced in CD1a- MoDCs. Differentiation upon F1 and F2 stimulation induced mixed profile of inflammatory cytokines. Altogether, these data demonstrate that Pb cell wall fractions differentially induce a dysregulation in DCs differentiation. Moreover, our results suggest that cell wall α-glucan promote the differentiation of CD1a- DCs, potentially favoring Th2 polarization and contributing to pathogen persistence.

Keywords: Paracoccidioidomycosis, Cell wall fractions, alfa-Glucan, Dendritic cell differentiation, Paracoccidioides brasiliensis

Received: 15 Jul 2019; Accepted: 11 Oct 2019.

Copyright: © 2019 Souza, Favali, Soares, Machado, Jeronimo, Veloso Junior, Marina, Santos, Brodskyn and Bocca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Anamelia L. Bocca, University of Brasilia, Brasilia, 70910-900, Distrito Federal, Brazil, albocca@unb.br