Schistosoma mansoni activates host microvascular endothelial cells to acquire an anti-inflammatory phenotype

Since endothelial cells (ECs) play a key role in immune defense mechanisms and in immunopathology, we investigated whether the intravascular helminth parasite Schistosoma mansoni could interact with and activate resting ECs i n vitro. Microscopic analysis revealed that the lung-stage schistosomula sp ecifically attached to microvascular ECs. This adherence was associated to active cellular processes involving actin filament formation, Since variati on of permeability of cultured capillary brain ECs is a good marker for end othelial activation, the transendothelial passage of a low-molecular-weight molecule (inulin) on monolayers of bovine brain capillary ECs (BBCEC) was measured in response to parasites. Schistosomula induced a dramatic decreas e in transendothelial permeability, a characteristic marker for the generat ion of an anti-inflammatory phenotype to ECs, This paracellular barrier enh ancing effect on endothelial monolayers was due to a soluble substance(s) ( below 1 kDa in size) secreted from S. mansoni schistosomula and not by mech anisms associated to adherence between parasites and ECs. The reinforcement of the endothelial barrier function was accompanied by an elevation of int racellular concentration of cyclic AMP (cAMP), The use of specific kinase i nhibitors confirms that schistosomula activate ECs through a cAMP/protein k inase A pathway that leads to an increased phosphorylation of the myosin li ght chain kinase. These combined findings suggest that the secretory/excret ory products from schistosomula possess anti-inflammatory factor(s) that si gnal host microvascular endothelium, The immunological consequences of such activation are discussed.