Interaction between Wolbachia and the fibrinolytic system as a possible pathological mechanism in cardiopulmonary dirofilariosis

Abstract

Dirofilaria immitis is a mosquito-borne parasite that produces an inflammatory process in the wall of the blood vessels of its definitive host during cardiopulmonary dirofilariosis, known as proliferative endarteritis. Parasite antigens participate in the appearance of this inflammatory event, among other mechanisms through the over-activation of the host fibrinolytic system. Since Wolbachia, endosymbiont bacteria of filarial nematodes, is released into the vertebrate host when worms die, the aim of this work was to analyse the interaction between this bacteria and the host fibrinolytic system to complete the study of this part of the host-parasite relationships. For that purpose, the recombinant form of the major Wolbachia surface protein (rWSP) was cloned, sequenced and expressed and then, its ability to bind plasminogen and enhance the generation of plasmin was assessed. We demonstrated that rWSP is a conserved antigen within the family Onchocercidae with ability to bind plasminogen and stimulate plasmin generation in a tissue-plasminogen activator (t-PA) and lysine residues of the rWSP-dependent manner. These results indicate that the recruitment of plasminogen by Wolbachia and the possible excess of plasmin generated could contribute to exacerbate the pathological events occurred at the vascular level during cardiopulmonary dirofilariosis, as well as in other diseases caused by filarial nematodes that harbour Wolbachia, when the bacteria is released after the death of the worms.