Role of complement and Fc{gamma} receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus.
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.
Moalli
Federica
F
Laboratory of Immunology and Inflammation, Istituto Clinico Humanitas, IRCCS, Rozzano, Milan, Italy.
Doni
Andrea
A
Deban
Livija
L
Zelante
Teresa
T
Zagarella
Silvia
S
Bottazzi
Barbara
B
Romani
Luigina
L
Mantovani
Alberto
A
Garlanda
Cecilia
C
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
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