The proteome of human adult whipworm Trichuris trichiura: A source of potential immunomodulatory molecules

Abstract

Soil-transmitted helminths (STHs), including Trichuris trichiura, pose a major global health challenge, particularly in children, causing significant morbidity. However, T. trichiura's ability to modulate host immune responses offers a unique opportunity to discover biomolecules with therapeutic potential for inflammatory, allergic, and autoimmune disorders. This study conducted a proteomic analysis of adult male and female T. trichiura using liquid chromatography-tandem mass spectrometry (LC-MS/MS), identifying 810 parasite proteins. Of these, 177 were exclusive to females, 277 to males, and 356 shared.

Gene ontology analysis showed similar cellular component profiles in males and females, mostly involving intracellular structures. However, female-exclusive proteins exhibited more diverse components. Molecular function analysis highlighted hydrolytic and catalytic activities, suggesting enzymatic strategies for nutrition and immune modulation. Notably, immunomodulatory proteins were identified in both sexes, showing therapeutic potential, including a Kunitz protease inhibitor and glutamate dehydrogenase.

To evaluate immunomodulatory properties, one identified protein (rc4299) was tested on cultures of peripheral blood mononuclear cells (PBMCs) from allergic individuals. The recombinantly produced rc4299 increased IL-10 secretion, indicating potential for treating autoimmune and allergic diseases. This study uncovers the T. trichiura proteome and highlights promising therapeutic targets, emphasizing the parasite's complex interactions with the host immune system.