title: Ficolin-3 activity towards the opportunistic pathogen, Hafnia alvei.
abstract: Ficolin-3 (also called H-ficolin or Hakata antigen) is a complement-activating pattern recognition molecule, possessing a fibrinogen-like domain involved in carbohydrate binding. Amongst human ficolins, Ficolin-3 has the highest concentration in serum and is the most potent lectin pathway activator in vitro. Evidence for its physiological function is sparse, although its deficiency has been suggested to increase susceptibility to infections. The specificity of Ficolin-3 is poorly characterized and currently few ligands are known. Here we report agglutination of Hafnia alvei, a Gram-negative enteric commensal bacterium and opportunist pathogen, in the presence of recombinant Ficolin-3 and calcium. Ficolin-3 also augmented phagocytosis of H. alvei by macrophages and displayed bactericidal activity. Additionally, Ficolin-3 inhibited host cells' response to TLR4/MD-2/CD14-LPS dependent NF-κB activation. This is the first demonstration of protective activity of Ficolin-3 against a human bacterial pathogen. Although human Ficolin-3 does not recognise and bind to common pathogenic bacteria, it could be an important component of innate immunity providing protection, for example, from commensal flora that can cause extraintestinal, opportunistic infections.
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland; Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Michalski
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland. Electronic address: aswierzko@cbm.pan.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: St Swierzko
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lukasiewicz
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Man-Kupisinska
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Karwaciak
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Przygodzka
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Cedzynski
mesh_terms: D000371:Agglutination; D002460:Cell Line; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D020611:Hafnia alvei / Q000276:immunology*; D006801:Humans; D037102:Lectins / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D009894:Opportunistic Infections; D010587:Phagocytosis / Q000276:immunology
chemical_list: C109662:FCN3 protein, human; D006023:Glycoproteins; D037102:Lectins; D008070:Lipopolysaccharides
keywords: Complement; Ficolin-3; H-ficolin; Hafnia; Innate immunity; Lipopolysaccharide (LPS); Phagocytosis