Abstract Background Agaricus brasiliensis is a medicinal mushroom with immunomodulatory and antitumor activities attributed to the β-glucans presented in the polysaccharide fraction of its fruiting body. Since β-glucans enhance cellular immunoresponsiveness, in this study we aimed to evaluate the effect of an acid-treated polysaccharide-rich fraction (ATF) of A. brasiliensis on the ability of human monocytes to adhere/phagocyte C. albicans yeast cells, their expression of pattern recognition receptors and their ability to produce cytokines. Methods Adhesion/phagocytosis of FITC-labeled C. albicans was evaluated by flow cytometry. Cells were incubated with specific fluorochrome-labeled antibodies for TLR2 and 4, βGR and MR and also evaluated by flow cytometry. Monocytes were cultured with ATF, and culture supernatants were collected for analysis of in vitro cytokine production by ELISA (TNF-α, IL-1β, IL-12 and IL-10). Results ATF significantly increased the adherence/phagocytosis of C. albicans by monocytes and this was associated with enhanced expression of TLR2 and TLR4, while no effect was observed on βGR or MR. Moreover, expression of TLR4 and TLR2 was associated with higher levels of in vitro production of TNF-α and IL-1, respectively. Production of IL-10 was also increased by ATF treatment, but we found no association between its production and the expression of Toll-like receptors. Conclusion Our results provided us with evidence that A. brasiliensis polysaccharides affect human monocytes probably through the modulation of Toll-like receptors.

Os mecanismos utilizados pelo Paracoccidioides brasiliensis para sobreviver em células fagocitárias ainda não estão elucidados. O metabolismo celular férrico é muito importante para o crescimento de inúmeros patógenos intracelulares cuja capacidade de se multiplicarem em fagócitos mononucleares é dependente da disponibilidade intracelular do íon ferro. Assim, o objetivo deste trabalho foi investigar o papel do ferro intracelular sobre a capacidade do P. brasiliensis sobreviver em monócitos humanos. O tratamento de monócitos com deferoxamina, uma droga quelante, diminuiu a sobrevivência de leveduras do fungo de forma dose-dependente. O efeito inibidor da deferoxamina sobre a sobrevivência do P. brasiliensis foi revertido por transferrina saturada com ferro (holotransferrina) mas não por transferrina insaturada (apotransferrina). Estes resultados sugerem que a sobrevivência do P. brasiliensis em monócitos humanos é dependente do íon ferro.

The mechanisms used by Paracoccidioides brasiliensis to survive into phagocytic cells are not clear. Cellular iron metabolism is of critical importance to the growth of several intracellular pathogens whose capacity to multiply in mononuclear phagocytes is dependent on the availability of intracellular iron. Thus, the objective of this paper was to investigate the role of intracellular iron in regulating the capacity of P. brasiliensis yeast cells to survive within human monocytes. Treatment of monocytes with deferoxamine, an iron chelator, suppressed the survival of yeasts in a concentration-dependent manner. The effect of deferoxamine was reversed by iron-saturated transferrin (holotransferrin) but not by nonsaturated transferrin (apotransferrin). These results strongly suggest that P. brasiliensis survival in human monocytes is iron dependent.