Year: 2012
Type: article
Abstract: 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.
Source: PLoS Pathogens
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: Georgia Clinical and Translational Science Alliance, UBS Optimus Foundation, National Institutes of Health, University of California, San Francisco, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: Clinical and Translational Science Institute, G1821371521, G2244544234, G2690160998, Spectrum Stanford Center for clinical and Translational Research and Education, Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1, Stanford Global Health Consortium: Innovation, Design, Evaluation, and Action, G3322721267, Estrogenic Modulation of Genitourinary Epithelial-Probiotic Cross-Talk, Alternative macrophage activation limits immunopathology, G5410153582, G6252814899, Trefoil Factors Regulate Th2 Immunity, G6579510461, G758528517, G9000058261, G9000246096, Molecular and Cellular Immunobiology, G937853209
OpenAlex ID: W2024981949