Papel das metaloproteinases de matriz na inflamação granulomatosa intestinal na esquistossomose mansônica

Abstract

Schistosomiasis mansoni is a neglected parasitic disease caused by the helminth Schistosoma mansoni. This disease is closely correlated with poverty and causes high enterohepatic morbidity associated with intense granulomatous inflammatory reaction triggered by parasite eggs retained in the microcirculation of the liver and intestine. In schistosomal enteropathy, granulomatous inflammation is associated with intestinal erosion and S. mansoni eggs translocation into the intestinal lumen, resulting in fecal excretion of these eggs. This process is essential to complete the biological cycle involved in parasite transmission to host organisms. There is evidence that metalloproteinases (MMP) are involved in granulomatous inflammation and collagen dynamics in the target organs of S.mansoni eggs. However, the relationship between MMP and collagen accumulation with the intestinal retention and excretion of parasite eggs remains poorly understood. In this sense, the present study investigated whether doxycycline, a potent MMP inhibitor, is capable of modulating granulomatous inflammation and intestinal morphological remodeling to the point of influencing the dynamics between intestinal retention and eggs excretion in S. mansoni-infected mice. Overall, our findings indicated that doxycycline treatment subverts collagen dynamics in schistosomiasis. By attenuating MMP-2 and MMP-9 activity, this drug is able to potentiate collagen accumulation in the intestinal wall, tissue fibrosis and hinder S. mansoni eggs translocation. Although the collagen content did not show correlation with MMP activity, intestinal retention and fecal excretion of parasite eggs; these correlations were observed for doxycycline-treated animals. Thus, our study provides evidence that doxycycline is able to attenuate the environmental elimination of S. mansoni eggs by aggravating granulomatous inflammation and inhibiting MMP-2 and MMP-9 activity, events potentially associated with excessive collagen accumulation, which hinders eggs translocation through the wall to the intestinal lumen. Variations in intestinal collagen dynamics are relevant since they may represent changes in the environmental dispersion of S. mansoni eggs, bringing repercussions for parasite life cycle of and schistosomiasis propagation.