title: Binding and activation of human and mouse complement by Cryptosporidium parvum (Apicomplexa) and susceptibility of C1q- and MBL-deficient mice to infection.
abstract: Cryptosporidium parvum is a protozoan parasite (Apicomplexa) that causes gastrointestinal disease in animals and humans. Whereas immunocompetent hosts can limit the infection within 1 or 2 weeks, immunocompromised individuals develop a chronic, life-threatening disease. The importance of the adaptive cellular immune response, with CD4+ T-lymphocytes being the major players, has been clearly demonstrated. Several non-adaptive immune mechanisms have been suggested to contribute to the host defence, such as interferon-gamma (IFN-gamma) from NK cells, certain chemokines, beta-defensins and pro-inflammatory cytokines, but the influence of the complement systems has been less well studied. We analysed the in vitro binding and activation of the human and mouse complement systems and tested the susceptibility to infection in complement-deficient mouse strains. We found that C. parvum can activate both the classical and lectin pathways, leading to the deposition of C3b on the parasite. Using real-time PCR, parasite development could be demonstrated in adult mice lacking mannan-binding lectin (MBL-A/C-/-) but not in mice lacking complement factor C1q (C1qA-/-) or in wild type C57BL/6 mice. The contribution of the complement system and the lectin pathway in particular to the host defence against cryptosporidiosis may become apparent in situations of immunodeficiency such as HIV infections or in early childhood.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Johannes Gutenberg-University Mainz, Augustusplatz/Hochhaus, D-55101 Mainz, Germany. fpetry@uni-mainz.de
authors.forename: Franz
authors.initials: F
authors.lastname: Petry
authors.forename: Vera
authors.initials: V
authors.lastname: Jakobi
authors.forename: Swen
authors.initials: S
authors.lastname: Wagner
authors.forename: Tesfaye Sisay
authors.initials: TS
authors.lastname: Tessema
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.forename: Michael
authors.initials: M
authors.lastname: Loos
mesh_terms: D000818:Animals; D002417:Cattle; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D015922:Complement C1q / Q000172:deficiency*; D003179:Complement C3b / Q000276:immunology; D003457:Cryptosporidiosis / Q000276:immunology* / Q000469:parasitology*; D016785:Cryptosporidium parvum / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004198:Disease Susceptibility; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D037601:Mannose-Binding Lectin / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D033661:Oocysts / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012965:Sodium Chloride / Q000494:pharmacology; D013696:Temperature
chemical_list: D037601:Mannose-Binding Lectin; D015800:Protozoan Proteins; D012333:RNA, Messenger; D012965:Sodium Chloride; D015922:Complement C1q; D003179:Complement C3b