title: Macrophages are required for host survival in experimental urogenital schistosomiasis.
abstract: Urogenital schistosomiasis, Schistosoma haematobium worm infection, afflicts millions of people with egg-triggered, fibrotic bladder granulomata. Despite the significant global impact of urogenital schistosomiasis, the mechanisms of bladder granulomogenesis and fibrosis are ill defined due to the prior lack of tractable animal models. We combined a mouse model of urogenital schistosomiasis with macrophage-depleting liposomal clodronate (LC) to define how macrophages mediate bladder granulomogenesis and fibrosis. Mice were injected with eggs purified from infected hamsters or vehicle prepared from uninfected hamster tissues (xenoantigen and injection trauma control). Empty liposomes were controls for LC: 1) LC treatment resulted in fewer bladder egg granuloma-infiltrating macrophages, eosinophils, and T and B cells, lower bladder and serum levels of eotaxin, and higher bladder concentrations of IL-1α and chemokines (in a time-dependent fashion), confirming that macrophages orchestrate leukocyte infiltration of the egg-exposed bladder; 2) macrophage-depleted mice exhibited greater weight loss and bladder hemorrhage postegg injection; 3) early LC treatment postegg injection resulted in profound decreases in bladder fibrosis, suggesting differing roles for macrophages in fibrosis over time; and 4) LC treatment also led to egg dose-dependent mortality, indicating that macrophages prevent death from urogenital schistosomiasis. Thus, macrophages are a potential therapeutic target for preventing or treating the bladder sequelae of urogenital schistosomiasis.
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford University, Stanford, California, USA;
authors.forename: Chi-Ling
authors.initials: CL
authors.lastname: Fu
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA;
authors.forename: Justin I
authors.initials: JI
authors.lastname: Odegaard
authors.affiliation: Biomedical Research Institute, Rockville, Maryland, USA; Children's National Medical Center, Washington, District of Columbia, USA; and The George Washington University, Washington, District of Columbia, USA mhsieh@afbr-bri.com.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D004002:Clodronic Acid / Q000008:administration & dosage; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D006099:Granuloma / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000502:physiology; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012553:Schistosomiasis haematobia / Q000469:parasitology / Q000473:pathology* / Q000503:physiopathology; D001745:Urinary Bladder Diseases / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology
chemical_list: D016207:Cytokines; D008081:Liposomes; D004002:Clodronic Acid
keywords: clodronate