A novel mouse model of Schistosoma haematobium egg-induced immunopathology

• Published in: PLoS pathogens Vol. 8; no. 3; p. e1002605
• Main Authors: Fu, Chi-Ling, Odegaard, Justin I, Herbert, De'Broski R, Hsieh, Michael H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2012; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Bladder; Cytokines; Disease Models, Animal; Excretory system; Female; Gene expression; Granuloma - immunology; Granuloma - parasitology; Granuloma - pathology; Health aspects; Host-Parasite Interactions; Immunopathology; Infections; Medicine; Mice; Mice, Inbred BALB C; Ovum - immunology; Parasite Egg Count; Physiological aspects; Schistosoma; Schistosoma haematobium - immunology; Schistosoma haematobium - pathogenicity; Schistosomiasis - complications; Schistosomiasis - immunology; Schistosomiasis - pathology; Tropical diseases; Urinary Bladder - immunology; Urinary Bladder - parasitology; Urinary Bladder - pathology; Urinary Tract Infections - parasitology; Urinary Tract Infections - pathology; Urogenital system; Urogenital System - immunology; Urogenital System - parasitology; Urogenital System - pathology; Virulence (Microbiology); Worms; United States; Granuloma; Schistosoma haematobium; Parasite Egg Count; Urogenital System; Schistosomiasis; Animals; Urinary Tract Infections; Female; Mice; Mice, Inbred BALB C; Ovum; Host-Parasite Interactions; Urinary Bladder; Disease Models, Animal
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1002605

Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. While humans readily develop urogenital schistosomiasis, the lack of an experimentally-tractable model has greatly impaired our understanding of the mechanisms that underlie this important disease. We have developed an improved mouse model of S. haematobium urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified S. haematobium eggs into the bladder wall, mice consistently develop macrophage-rich granulomata that persist for at least 3 months and pass eggs in their urine. Importantly, egg-injected mice also develop urinary tract fibrosis, bladder dysfunction, and various urothelial changes morphologically reminiscent of human urogenital schistosomiasis. As expected, S. haematobium egg-induced immune responses in the immediate microenvironment, draining lymph nodes, and systemic circulation are associated with a Type 2-dominant inflammatory response, characterized by high levels of interleukin-4, eosinophils, and IgE. Taken together, our novel mouse model may help facilitate a better understanding of the unique pathophysiological mechanisms of epithelial dysfunction, tissue fibrosis, and oncogenesis associated with urogenital schistosomiasis.