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. 2001 Aug;69(8):4846-50.
doi: 10.1128/IAI.69.8.4846-4850.2001.

Immunoglobulin A-mediated protection against Bordetella pertussis infection

S M Hellwig  1 , A B van Spriel, J F Schellekens, F R Mooi, J G van de Winkel
Affiliations

Immunoglobulin A-mediated protection against Bordetella pertussis infection

S M Hellwig et al. Infect Immun. 2001 Aug.

Abstract

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.

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Figures

FIG. 1
FIG. 1
Binding of IgA and BsAb to B. pertussis and PMNL. (A) B. pertussis was incubated with IgA, and binding was visualized by incubation with FITC-conjugated anti-human IgA (black line). FITC-conjugated anti-human IgA alone was used as a control (dotted line). Bacteria were gated based on their scatter characteristics. (B) B. pertussis and PMNL were incubated with CD89 BsAb directed against FcαRI. Binding was visualized with FITC-conjugated anti-rabbit IgG (□, ○) or FITC-conjugated anti-mouse IgG (▪, ●). Data are representative of those from three separate experiments. Conc, concentration.
FIG. 2
FIG. 2
IgA induces B. pertussis phagocytosis by PMNL. (A) Mouse PMNL Tg for the human IgA receptor were incubated with PKH-26-labeled and IgA-opsonized B. pertussis at 4°C for 30 min. Nonadherent bacteria were removed, and PMNL were further incubated for 30 min at either 4 or 37°C to allow phagocytosis. Subsequently, surface-bound B. pertussis cells were detected by incubation with FITC-conjugated F(ab′)2 fragments. Viable PMNL were gated based on their scatter characteristics, and a reduction of FITC fluorescence reflects uptake of B. pertussis by PMNL. (B) Phagocytosis was expressed in arbitrary units (AU). (C) Phagocytosis of IgA-opsonized B. pertussis by human PMNL in the absence (control) or presence of FcαRI-blocking antibody 2D11. Data are representative of those from at least three individual experiments and are depicted as means and standard errors of the means. ∗, P < 0.05.
FIG. 3
FIG. 3
Bactericidal activity mediated by mouse PMNL Tg for the human FcαRI. FcαRI-Tg and NTg mouse PMNL were incubated with nonopsonized B. pertussis or B. pertussis opsonized with CD89 BsAb. Numbers of killed bacteria per 105 PMNL were determined after 30 min. Bars represent means and standard deviations of killed bacteria from one representative experiment out of three. ∗, P < 0.05.
FIG. 4
FIG. 4
In vivo targeting to human FcαRI enhances B. pertussis clearance in FcαRI-Tg mice. Tg and NTg mice were infected intranasally with B. pertussis that was either nonopsonized or opsonized with serum IgA. The control group, consisting of both Tg and NTg mice, was infected with nonopsonized bacteria. Two days after infection, lungs were excised and homogenized, and the numbers of viable bacteria were determined. Each bar represents the mean number of log10 CFU from at least 12 mice tested in two individual experiments. Error bars indicate standard errors of the means. ∗, P < 0.05.
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