title: Role of Paracoccidioides brasiliensis cell wall fraction containing beta-glucan in tumor necrosis factor-alpha production by human monocytes: correlation with fungicidal activity.
abstract: The polysaccharide fraction of Paracoccidioides brasiliensis mycelial cell wall (F1 fraction), the active component of which is composed of beta-glucan, was investigated in regard to the activation of human monocytes for fungal killing. The cells were primed with interferon-gamma (IFN-gamma) or F1 (100 and 200 microg ml(-1)) or F1 (100 and 200 microg ml(-1)) plus IFN-gamma for 24 h and then evaluated for H2O2 release. In other experiments, the cells were pretreated with the same stimuli, challenged with a virulent strain of P. brasiliensis and evaluated for fungicidal activity and levels of tumor necrosis factor (TNF-alpha) in the supernatants. F1 increased the levels of H2O2 in a similar manner to IFN-gamma. However, a synergistic effect between these two activators was not detected. On the contrary, a significant fungicidal activity was only obtained after priming with IFN-gamma plus F1. This higher activity was associated with high levels of TNF-alpha in the supernatants of the cocultures. Overall, P. brasiliensis F1 fraction induced human monocytes to release relatively high levels of TNF-alpha, which, in combination with IFN-gamma, is responsible for the activation of human monocytes for effective killing of P. brasiliensis.
authors.forename: A R
authors.initials: AR
authors.lastname: Anjos
authors.forename: S A
authors.initials: SA
authors.lastname: Calvi
authors.forename: R
authors.initials: R
authors.lastname: Ferracini
authors.forename: M T S
authors.initials: MT
authors.lastname: Peraçoli
authors.forename: C L
authors.initials: CL
authors.lastname: Silva
authors.forename: A M V C
authors.initials: AM
authors.lastname: Soares
mesh_terms: D018929:Cell Culture Techniques; D002473:Cell Wall / Q000276:immunology; D005936:Glucans / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016260:Monocytes, Activated Killer / Q000187:drug effects* / Q000276:immunology; D010228:Paracoccidioides / Q000737:chemistry*; D010229:Paracoccidioidomycosis / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D005936:Glucans; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma