Aspectos histopatológicos e imunológicos do desenvolvimento do granuloma esquistossomótico na coinfecção por Schistosoma mansoni E Paracoccidioides brasiliensis em modelo murino.

Abstract

Schistosomiasis, also known as snail fever, a disease caused by the parasite Schistosoma mansoni, is a worldwide health issue. Paracoccidioidomycosis (PCM) is a human systemic mycosis caused by the fungus Paracoccidioides brasiliensis and it may coinfect the bearing host of S. mansoni. In the coinfection by S. mansoni, the host immune system may be suppressed which results in an insufficient defense in order to obliterate other microorganisms. There are few studies so far describing the evolution of schistosomiasis and paracoccidioidomycosis in the case of coinfection. Furthermore, due to migration, people from schistosomiasis endemic areas may settle down in PCM endemic areas and vice versa. Considering the given background, this study had as main goal the analysis of histopathological and immunological aspects of the development of schistosomotic granuloma under the coinfection. Thereunto, Swiss female mice were separated in four groups for acute phase and five groups for chronic phase containing ten animals each: control not infected - CNI, infected with S. mansoni - Sm, infected with P. brasiliensis - Pb, coinfected – Sm+Pb, both in chronic phase, and coinfected Sm in chronic phase and Pb in acute phase – Sm(c)+Pb(a). The mice were necropsied after 50 days (acute phase) and 120 days (chronic phase) for analysis concerning their weight, survival rate, granuloma development and cytokine production. Regarding the weight, it was observed the Pb group had gained significantly weight (26,23±5,36g). Concerning the survival rate, in acute phase, it was observed 10% of deaths in the Sm group; as for the chronic phase, 50% of deceased for Sm group, 60% for Sm+Pb group and 50% for Sm(c)+Pb(a) by the end of the experiment. The coinfection occurrence was demonstrated by granuloma visualization in the liver and lung, and presence of the fungus in the omentum. The granuloma count in the liver (acute and chronic phases) and lung (chronic phase) did not display any meaningful differences. Regarding the diameter of the granulomas in the liver in acute phase, it was meaningfully bigger than Sm group (0,08±0,05 mm²) when compared to Sm+Pb group (0,06±0,05mm²). In the chronic phase, the diameter was quite bigger when compared to Sm+Pb (0,03±0,01mm²) and Sm(c)+Pb(a) (0,02±0,01mm²) groups. Toward the lung , there were high significant differences when compared Sm groups (0.01 ± 0,009mm²) with Sm+Pb (0.03 ± 0,01mm² ) and Sm(C)+Pb(A) (0.03 ± 0,02mm²) .Mononuclear and polymorphnuclear cells of liver and lung granulomas were evidenced in all groups both in acute and chronic phases. In acute phase, the eosinophil and neutrophils counts did not have meaningful distinctions regarding the cell types, although a bigger number of neutrophils were observed in Sm+Pb group (7,82±5,95). In chronic phase, it was verified a distinguished prevalence of eosinophils (17,34±6,71) in Sm group, whilst Sm+Pb and Sm(c)+Pb(a) groups neutrophils prevailed (18,82±8,18 e 12,72±4,44, respectively). In the lung, there were not any differences in regard of eosinophil number in granulomas, while the number of neutrophils in Sm(c)+Pb(a) group (2,66±2,71) was really smaller than Sm (9,62±7,76) and Sm+Pb (8,06±5,40) groups. The results of cytokine analysis from those different groups display a distinguished augmentation of IFN-γ in Sm (8,05±3,52ng/ml) and Pb (10,40±3,549ng/ml) groups regarding the CNI (1,14±0,48 ng/ml), however this increase observed in Sm+Pb group (4,96±1,73ng/ml) wasn’t meaningful at all. The cytokine IL-2 displayed notably higher levels in Sm (6,71±1,50ng/ml), Pb (10,40 3,54±ng/ml) and Sm+Pb groups (7,32±2,93ng/ml) when compared to CNI (2,01± 0,39ng/ml). As for IL-4, there were expressive high differences between Sm (10,45±3,67ng/ml), Pb (3,98±1,76 ng/ml) and Sm+Pb groups (4,28±2,22ng/ml) regarding CNI (0,67±0,21ng/ml). For IL-5, significant differences were found in groups Sm (3.91 ± 0,61ng / ml), Pb (3.98 ± 1.76 ng / ml) and Sm + Pb (4.28 ± 2,22ng / ml) compared to the CNI (0.67 ± 0,21ng / ml). In chronic phase, it was observed denoting high levels of IFN-γ in Sm group (10,45± 3,67ng/ml) when compared to CNI (1,14±0,48ng/ml). Concerning IL-2, there were compelling differences from Sm (7,90±3,16ng/ml) and Pb groups (7,54±1,41ng/ml), in regard of CNI (2,01±0,39ng/ml). As for IL-4 and IL-5, expressively high distinctions were observed in Sm (8,46±3,71ng/ml and 4,47±1,88ng/ml, respectively) concerning CNI (0,85±0,15ng/ml and 0,67± 0,21 ng/ml, respectively). Regarding MIP-2, it was not observed any important differences among the groups as for the acute or chronic phases, nevertheless these display higher levels in acute phase rather than in chronic phase. Thus, the data suggest the coinfection by P. brasiliensis may affect the cellular composition from schistosomotic granulomas and cytokine levels.