Targeting to Fc gamma receptors, but not CR3 (CD11b/CD18), increases clearance of Bordetella pertussis

In the absence of opsonizing antibodies, Bordetella pertussis, the causativ e agent of pertussis, readily binds to phagocytes via complement receptor 3 (CR3). After opsonization with antibodies, binding is mediated by IgG rece ptors (Fc gammaR). The effect of targeting B. pertussis to either Fc gammaR or CR3 was studied. The fate of unopsonized B. pertussis, IgG-opsonized B. pertussis, and B. pertussis opsonized with bispecific antibodies (BsAbs) d irected to CR3 or Fc gamma RII/-III was compared. IgG antibodies mediated b inding and phagocytosis of B. pertussis via Fc gammaR by polymorphonuclear leukocytes (PMNL) in vitro. Opsonization of B. pertussis with BsAbs directe d against either CR3 or Fc gamma RII/-III facilitated PMNL phagocytosis; ho wever, in vivo studies with BsAb revealed that Fc gammaR-mediated uptake fa cilitates B. pertussis clearance, in contrast to uptake via CR3. Targeting of B. pertussis to Fc gamma RII/-III in mice deficient in Fc gamma RII or F c gamma RIII indicated that the protective effect is attributable to Fc gam ma RIII. Competition between uptake via CR3 or Fc gammaR may determine the outcome of natural infection.