Experimental trichuriasis: Changes in the immune response and bacterial translocation during acute phase development illustrated with 3D model animation

Trichuriasis, a well-known type of soil-transmitted helminthiasis, is a neglected gastrointestinal nematode disease predominantly affecting children in tropical regions and is caused by Trichuris trichiura. The potential zoonotic transmission of this disease is indicated by its presence in nonhuman primates. Chronic infection leads to mucosal damage, bacterial translocation, and intense inflammatory infiltration; however, the progression of these processes remains poorly understood. This study tracks the acute phase of experimental trichuriasis, providing detailed insights into nematode tissue migration stages, inflammatory infiltration, cytokine production, and 2D/3D imaging of the bacterial translocation process. We showed a mixed immune response (Th1, Th2, and Th17) initiated by larval-induced lesions in the intestine tissue and modulated by L4 larvae and adult worms in the cecum, with systemic changes observed in the mesenteric lymph nodes, peritoneal macrophages, and spleen. Despite the disruption of the intestinal mucosa within the first 10 days post-infection (d.p.i.), bacterial invasion becomes evident only after the development of the nematode into the L3 larval stage (17 d.p.i.), intensifying with lesions caused by the L4 larvae (22 d.p.i.) and adult worms (35 d.p.i.). Our multidimensional approach, which incorporates microscopy tools, micro-CT, physiological evaluations, tissue/organ assessments, and immunological parameters, demonstrates the ability of larvae to breach the intestinal mucosa, further indicating the timing of extensive bacterial infiltration. Additionally, a 3D animation illustrates how adult worm attachment mechanisms may facilitate bacterial translocation. This study provides significant insights into the immunological and pathological mechanisms of trichuriasis progression, highlighting the complex interplay among host immune responses, the gut microbiome, and parasite survival strategies, all of which are crucial aspects for future therapeutic development.