Abstract
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 7 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.
Highlights
The cell wall is a complex and dynamic structure that plays essential roles in fungal cell biology
Our results demonstrate that both alkali-insoluble β-glucan rich (F1) and alkali-soluble α-glucan rich (F2) cell wall fractions differentially alter in vitro differentiation of human monocyte-derived dendritic cells (DCs) regarding the expression of HLA-DR, DC-SIGN, CD83, and CD80 molecules, and their ability to secrete inflammatory cytokines
Paracoccidioides brasiliensis yeast cell wall is organized in an inner layer, mostly composed by β-glucan, chitin and proteins, and an outermost layer, which is mainly composed by α-glucan (Moreno et al, 1969; Carbonell et al, 1970; Kanetsuna and Carbonell, 1970; Puccia et al, 2011)
Summary
The cell wall is a complex and dynamic structure that plays essential roles in fungal cell biology. Cell shape, polarized growth, sensing of, response to or protection against surrounding conditions and interaction with the extracellular environment are some of the processes fully dependent on a healthy fungal cell wall. This organelle is a polysaccharide-rich shield that surrounds the outer face of the phospholipidic cell membrane, and its molecular composition and structure varies according to fungal species, morphotype and life cycle. Cell wall components are mostly absent in animals and plants For this reason, it is an important target for the development of antifungal therapy and its contribution to host immune responses has been vastly investigated. The composition and structure of the fungal cell wall have been described in several other review papers (Bowman and Free, 2006; Latgé, 2010; Free, 2013; Gow et al, 2017)
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