Detrimental Effect Of Fungal 60-kda Heat Shock Protein On Experimental Paracoccidioides Brasiliensis Infection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The genus Paracoccidioides comprises species of dimorphic fungi that cause paracocci-dioidomycosis (PCM), a systemic disease prevalent in Latin America. Here, we investigated whether administration of native 60-kDa heat shock protein of P. brasiliensis (nPbHsp60) or its recombinant counterpart (rPbHsp60) affected the course of experimental PCM. Mice were subcutaneously injected with nPbHsp60 or rPbHsp60 emulsified in complete's Freund Adjuvant (CFA) at three weeks after intravenous injection of P. brasiliensis yeasts. Infected control mice were injected with CFA or isotonic saline solution alone. Thirty days after the nPbHsp60 or rPbHsp60 administration, mice showed remarkably increased fungal load, tissue inflammation, and granulomas in the lungs, liver, and spleen compared with control mice. Further, rPbHsp60 treatment (i) decreased the known protective effect of CFA against PCM and (ii) increased the concentrations of IL-17, TNF-alpha, IL-12, IFN-gamma, IL-4, IL-10, and TGF-beta in the lungs. Together, our results indicated that PbHsp60 induced a harmful immune response, exacerbated inflammation, and promoted fungal dissemination. Therefore, we propose that PbHsp60 contributes to the fungal pathogenesis.119Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2009/14777-1, 2013/12278-3, 2009/03235-3, 2012/08552-0]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Geoqu?mica de is?topos est?veis (C, S e O) das rochas encaixantes e do min?rio de Cu(Au) do dep?sito cristalino, prov?ncia mineral de Caraj?s, Par?.

Descrevemos dados de is?topos est?veis de rochas encaixantes e de min?rios sulfetados do dep?sito de Cu(Au) do Cristalino (DC), Prov?ncia Caraj?s, Brasil. Analisamos calcita de rocha total e de sulfetos de vulc?nicas m?ficas a f?lsicas e ?brechas hidrotermais?. O DC, um dep?sito arqueano (ca. 2.7Ga) IOCG, ocorre em supracrustais hidrotermalizadas (e.g., alcaliniza??o; carbonata??o; sulfeta??o; etc.) do Supergrupo Itacai?nas. Dioritos cortam estas rochas e podem relacionar ao min?rio de Cu. Assinaturas isot?picas de ?34S e ?13C e ?18O plotam nos sulfetos do manto e campo prim?rio dos carbonatitos, respectivamente. Os fluidos do min?rio podem ser derivados de uma intrus?o gran?tica ou dior?tica ou lixiviados de rochas vulc?nicas m?ficas do tipo-MORB.We describe stable isotopic data from country rocks and sulfide ores of the Cristalino Cu(Au) deposit (CD), Caraj?s Province, Brazil. Calcite from whole rock and sulfides grains from mafic to felsic volcanics and ?hydrothermal breccias? were analyzed. The CD, an Archean (ca. 2.7Ga) IOCG deposit, occurs in hydrothermalized (e.g., alkalinization; carbonatization; sulfidation; etc.) Itacai?nas Supergroup supracrustals. Diorites crosscut these rocks and can relate to Cu-ore. Isotopic signatures of ?34S and ?13C and ?18O plot in the mantle sulfides and in the carbonatite primary field respectively. Ore fluids may be derived from a granitic or dioritic intrusion or leached from MORB-type mafic volcanic rocks

Detrimental effect of fungal 60-kDa heat shock protein on experimental Paracoccidioides brasiliensis Infection

The genus Paracoccidioides comprises species of dimorphic fungi that cause paracocci-dioidomycosis (PCM), a systemic disease prevalent in Latin America. Here, we investigated whether administration of native 60-kDa heat shock protein of P. brasiliensis (nPbHsp60) or its recombinant counterpart (rPbHsp60) affected the course of experimental PCM. Mice were subcutaneously injected with nPbHsp60 or rPbHsp60 emulsified in complete's Freund Adjuvant (CFA) at three weeks after intravenous injection of P. brasiliensis yeasts. Infected control mice were injected with CFA or isotonic saline solution alone. Thirty days after the nPbHsp60 or rPbHsp60 administration, mice showed remarkably increased fungal load, tissue inflammation, and granulomas in the lungs, liver, and spleen compared with control mice. Further, rPbHsp60 treatment (i) decreased the known protective effect of CFA against PCM and (ii) increased the concentrations of IL-17, TNF-alpha, IL-12, IFN-gamma, IL-4, IL-10, and TGF-beta in the lungs. Together, our results indicated that PbHsp60 induced a harmful immune response, exacerbated inflammation, and promoted fungal dissemination. Therefore, we propose that PbHsp60 contributes to the fungal pathogenesis119FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2009/14777-1; 2013/12278-3; 2009/03235-3; 2012/08552-