Date Published: October 29, 2008
Publisher: Public Library of Science
Author(s): Yovany Moreno, Timothy G. Geary, Elodie Ghedin
Abstract: IntroductionWhile we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection.Methodology/Principal FindingsTo gain a deeper understanding on these aspects, we collected and analyzed through 1D-SDS PAGE and LC-MS/MS the Excretory-Secretory Products (ESP) of adult female, adult male and microfilariae of the filarial nematode Brugia malayi, one of the etiological agents of human lymphatic filariasis. This proteomic analysis led to the identification of 228 proteins. The list includes 76 proteins with unknown function as well as also proteins with potential immunoregulatory properties, such as protease inhibitors, cytokine homologues and carbohydrate-binding proteins. Larval and adult ESP differed in composition. Only 32 proteins were shared between all three stages/genders. Consistent with this observation, different gene ontology profiles were associated with the different ESP.Conclusions/SignificanceA comparative analysis of the proteins released in vitro by different forms of a parasitic nematode dwelling in the same host is presented. The catalog of secreted proteins reflects different stage- and gender-specific related processes and different strategies of immune evasion, providing valuable insights on the contribution of each form of the parasite for establishing the host–parasite interaction.
Partial Text: Lymphatic filariasis (LF) is a disabling and disfiguring parasitic disease caused by the adult and developing forms of filarial nematode parasites residing in the lymphatic system of a mammalian host. The infection in humans is caused by Wuchereria bancrofti, Brugia malayi or B. timori and puts at risk an estimated 1307 million people in 83 endemic countries in subtropical and tropical regions of the world .
Filarial infections pose continuing and significant threats to human and animal health. Although drugs such as ivermectin, diethylcarbamazine (DEC) and albendazole are currently used to interrupt disease transmission and reduce morbidity , there are concerns about the emergence of resistance for these drugs ,. Secreted products are thought to be essential for the establishment of the parasitic lifestyle and therefore their identification in filarial nematodes may lead to the discovery of novel drug and vaccine targets –. Moreover, their recognition will help to illuminate the biology of secretory processes in these organisms and to establish a path for developing a deeper understanding of how parasite proteins function in immune evasion.