Trichuris trichiura egg extract proteome reveals potential diagnostic targets and immunomodulators

Embryonated eggs are the infectious developmental stage of Trichuris trichiura and are the primary stimulus for the immune system of the definitive host. The intestinal-dwelling T. trichiura affects an estimated 465 million people worldwide with an estimated global burden of disease of 640 000 DALYs (Disability Adjusted Life Years). In Latin America and the Caribbean, trichuriasis is the most prevalent soil transmitted helminthiasis in the region (12.3%; 95% CI). The adverse health consequences impair childhood school performance and reduce school attendance resulting in lower future wage-earning capacity. The accumulation of the long-term effects translates into poverty promoting sequelae and a cycle of impoverishment. Each infective T. trichiura egg carries the antigens needed to face the immune system with a wide variety of proteins present in the shell, larvae's surface, and the accompanying fluid that contains their excretions/secretions. We used a proteomic approach with tandem mass spectrometry to investigate the proteome of soluble non-embryonated egg extracts of T. trichiura obtained from naturally infected African green monkeys (Chlorocebus sabaeus). A total of 231 proteins were identified, 168 of them with known molecular functions. The proteome revealed common proteins families which are known to play roles in energy and metabolism; the cytoskeleton, muscle and motility; proteolysis; signaling; the stress response and detoxification; transcription and translation; and lipid binding and transport. In addition to the study of the T. trichiura non-embryonated egg proteome, the antigenic profile of the T. trichiura non-embryonated egg and female soluble proteins against serum antibodies from C. sabaeus naturally infected with trichuriasis was investigated. We used an immunoproteomic approach by Western blot and tandem mass spectrometry from the corresponding SDS-PAGE gels. Vitellogenin N and VWD and DUF1943 domain containing protein, poly-cysteine and histidine tailed protein isoform 2, heat shock protein 70, glyceraldehyde-3-phosphate dehydrogenase, actin, and enolase, were among the potential immunoactive proteins. To our knowledge, this is the first study on the T. trichiura non-embryonated egg proteome as a novel source of information on potential targets for immunodiagnostics and immunomodulators from a neglected tropical disease. This initial list of T. trichiura non-embryonated egg proteins (proteome and antigenic profile) can be used in future research on the immunobiology and pathogenesis of human trichuriasis and the treatment of human intestinal immune-related diseases. Author summary Who came first the worm or its egg? In the case of whipworm, we know it is the egg. The infective life cycle stage of the human whipworm (Trichuris trichiura) is the primary stimulus for the immune system of the definitive host. Each infective whipworm egg carries the information needed to face the immune system of the host with a wide variety of proteins present in the shell, larvae's surface, and the accompanying fluid that contains their excretions/secretions. We investigated the soluble proteins of the non-embryonated egg using an immunoproteomic approach and then selected the top five proteins using a series of bioinformatic analysis. We used these top five proteins to recognize potential targets for immunodiagnostics and immunomodulation while comparing them to known female worm proteins. We found that the proteins we selected were involved in lipid transport, energy and metabolism, and muscle and motility. One protein has unknown function.

Automated summary

Embryonated eggs of Trichuris trichiura play a crucial role in stimulating the immune system of the definitive host. Studies on the proteome and antigenic profile of non-embryonated eggs provide valuable information for potential immunodiagnostics and immunomodulators. The proteins identified in the study are involved in various biological functions, including lipid transport, energy metabolism, and muscle motility.