Immunoglobulin A-mediated protection against Bordetella pertussis infection.
Infection with Bordetella pertussis, the causative agent of pertussis (whooping cough) in humans, is followed by the production of antibodies of several isotypes, including immunoglobulin A (IgA). Little is known, however, about the role of IgA in immunity against pertussis. Therefore, we studied targeting of B. pertussis to the myeloid receptor for IgA, FcalphaRI (CD89), using either IgA purified from immune sera of pertussis patients or bispecific antibodies directed against B. pertussis and FcalphaRI (CD89 BsAb). Both IgA and CD89 BsAb facilitated FcalphaRI-mediated binding, phagocytosis, and bacterial killing by human polymorphonuclear leukocytes (PMNL) and PMNL originating from human FcalphaRI-transgenic mice. Importantly, FcalphaRI targeting resulted in enhanced bacterial clearance in lungs of transgenic mice. These data support the capacity of IgA to induce anti-B. pertussis effector functions via the myeloid IgA receptor, FcalphaRI. Increasing the amount of IgA antibodies induced by pertussis vaccines may result in higher vaccine efficacy.
Hellwig
S M
SM
Laboratory for Infectious Diseases Research, National Institute of Public Health and the Environment, Bilthoven, University Medical Center, Utrecht, The Netherlands.
van Spriel
A B
AB
Schellekens
J F
JF
Mooi
F R
FR
van de Winkel
J G
JG
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001886:Bordetella pertussis / Q000276:immunology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology*; D014917:Whooping Cough / Q000517:prevention & control*
D000907:Antibodies, Bacterial; D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc