Targeting to Fcgamma receptors, but not CR3 (CD11b/CD18), increases clearance of Bordetella pertussis.
In the absence of opsonizing antibodies, Bordetella pertussis, the causative agent of pertussis, readily binds to phagocytes via complement receptor 3 (CR3). After opsonization with antibodies, binding is mediated by IgG receptors (FcgammaR). The effect of targeting B. pertussis to either FcgammaR or CR3 was studied. The fate of unopsonized B. pertussis, IgG-opsonized B. pertussis, and B. pertussis opsonized with bispecific antibodies (BsAbs) directed to CR3 or FcgammaRII/-III was compared. IgG antibodies mediated binding and phagocytosis of B. pertussis via FcgammaR by polymorphonuclear leukocytes (PMNL) in vitro. Opsonization of B. pertussis with BsAbs directed against either CR3 or FcgammaRII/-III facilitated PMNL phagocytosis; however, in vivo studies with BsAb revealed that FcgammaR-mediated uptake facilitates B. pertussis clearance, in contrast to uptake via CR3. Targeting of B. pertussis to FcgammaRII/-III in mice deficient in FcgammaRII or FcgammaRIII indicated that the protective effect is attributable to FcgammaRIII. Competition between uptake via CR3 or FcgammaR may determine the outcome of natural infection.
Laboratory for Infectious Diseases. National Institute of Public Health and the Environment, Bilthoven, Utrecht, The Netherlands.
S M
SM
Hellwig
H F
HF
van Oirschot
W L
WL
Hazenbos
A B
AB
van Spriel
F R
FR
Mooi
J G
JG
van De Winkel
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D018033:Antibodies, Bispecific / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D014917:Whooping Cough / Q000276:immunology
D000907:Antibodies, Bacterial; D018033:Antibodies, Bispecific; D007074:Immunoglobulin G; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D017452:Receptors, IgG