title: Ficolins Promote Fungal Clearance in vivo and Modulate the Inflammatory Cytokine Response in Host Defense against Aspergillus fumigatus.
abstract: Aspergillus fumigatus is an opportunistic fungal pathogen that causes severe invasive infections in immunocompromised patients. Innate immunity plays a major role in protection against A. fumigatus. The ficolins are a family of soluble pattern recognition receptors that are capable of activating the lectin pathway of complement. Previous in vitro studies reported that ficolins bind to A. fumigatus, but their part in host defense against fungal infections in vivo is unknown. In this study, we used ficolin-deficient mice to investigate the role of ficolins during lung infection with A. fumigatus. Ficolin knockout mice showed significantly higher fungal loads in the lungs 24 h postinfection compared to wild-type mice. The delayed clearance of A. fumigatus in ficolin knockout mice could not be attributed to a compromised recruitment of inflammatory cells. However, it was revealed that ficolin knockout mice exhibited a decreased production of proinflammatory cytokines in the lungs compared to wild-type mice following A. fumigatus infection. The impaired clearance and cytokine production in ficolin knockout mice was independent of complement, as shown by equivalent levels of A. fumigatus-mediated complement activation in ficolin knockout mice and wild-type mice. In conclusion, this study demonstrates that ficolins are important in initial innate host defense against A. fumigatus infections in vivo.
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ninette
authors.initials: N
authors.lastname: Genster
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Præstekjær Cramer
authors.forename: Anne
authors.initials: A
authors.lastname: Rosbjerg
authors.forename: Katrine
authors.initials: K
authors.lastname: Pilely
authors.forename: Jack Bernard
authors.initials: JB
authors.lastname: Cowland
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D002478:Cells, Cultured; D037582:Complement Pathway, Mannose-Binding Lectin; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology*; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051192:Receptors, Pattern Recognition / Q000276:immunology / Q000378:metabolism*; D000097604:Ficolins
chemical_list: D016207:Cytokines; D037102:Lectins; D051192:Receptors, Pattern Recognition; D000097604:Ficolins