ABSTRACT
Paracoccidioides brasiliensis, a thermal dimorphic fungal pathogen, produces a melanin-like pigment in vitro and in vivo. We investigated the involvement of carbohydrates and monoclonal antibody to CD18, on phagocytosis inhibition, involving macrophage receptors and the resistance of melanized fungal cells to chemically generated nitric oxide (NO), reactive oxygen species (ROS), hypochlorite and H2O2. Our results demonstrate that melanized yeast cells were more resistant than nonmelanized yeast cells to chemically generated NO, ROS, hypochlorite and H2O2, in vitro. Phagocytosis of melanized yeast cells was virtually abolished when mannan, N-acetyl glucosamine and anti-CD18 antibody were added together in this system. Intratracheal infection of BALB/c mice, with melanized yeast cells, resulted in higher lung colony forming units, when compared to nonmelanized yeast cells. Therefore, melanin is a virulence factor of P. brasiliensis.
Subject(s)
Animals , Mice , Antifungal Agents/pharmacology , Macrophages/microbiology , Melanins/biosynthesis , Oxidants/pharmacology , Phagocytosis , Paracoccidioides/pathogenicity , Antibodies, Monoclonal/pharmacology , /drug effects , Carbohydrates/pharmacology , Mice, Inbred BALB C , Paracoccidioides/drug effects , Paracoccidioides/metabolism , Virulence Factors/physiologyABSTRACT
Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (~ 51.2 percent). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9 percent) appeared at the top of the list, followed by candidiasis (30.2 percent), histoplasmosis (10.1 percent) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.