title: Role of complement and Fc{gamma} receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus.
abstract: Pentraxin 3 (PTX3) is a soluble pattern recognition molecule playing a nonredundant role in resistance against Aspergillus fumigatus. The present study was designed to investigate the molecular pathways involved in the opsonic activity of PTX3. The PTX3 N-terminal domain was responsible for conidia recognition, but the full-length molecule was necessary for opsonic activity. The PTX3-dependent pathway of enhanced neutrophil phagocytic activity involved complement activation via the alternative pathway; Fcγ receptor (FcγR) IIA/CD32 recognition of PTX3-sensitized conidia and complement receptor 3 (CR3) activation; and CR3 and CD32 localization to the phagocytic cup. Gene targeted mice (ptx3, FcR common γ chain, C3, C1q) validated the in vivo relevance of the pathway. In particular, the protective activity of exogenous PTX3 against A fumigatus was abolished in FcR common γ chain-deficient mice. Thus, the opsonic and antifungal activity of PTX3 is at the crossroad between complement, complement receptor 3-, and FcγR-mediated recognition. Because short pentraxins (eg, C-reactive protein) interact with complement and FcγR, the present results may have general significance for the mode of action of these components of the humoral arm of innate immunity.
authors.affiliation: Laboratory of Immunology and Inflammation, Istituto Clinico Humanitas, IRCCS, Rozzano, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Moalli
authors.forename: Andrea
authors.initials: A
authors.lastname: Doni
authors.forename: Livija
authors.initials: L
authors.lastname: Deban
authors.forename: Teresa
authors.initials: T
authors.lastname: Zelante
authors.forename: Silvia
authors.initials: S
authors.lastname: Zagarella
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D002097:C-Reactive Protein / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology; D007113:Immunity, Innate; D016177:Macrophage-1 Antigen / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009895:Opsonin Proteins / Q000276:immunology; D011951:Receptors, Complement / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D051192:Receptors, Pattern Recognition; D015398:Signal Transduction / Q000276:immunology; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D016177:Macrophage-1 Antigen; D009419:Nerve Tissue Proteins; D009895:Opsonin Proteins; D011951:Receptors, Complement; D017452:Receptors, IgG; D051192:Receptors, Pattern Recognition; D000099153:Pentraxins