Effective phagocytosis and killing of Candida albicans via targeting FcγRI (CD64) or FcαRI (CD89) on neutrophils

Invasive fungal infections are an increasing problem for immunocompromised patients. As an approach to improve targeting of polymorphonuclear leukocytes (PMNL) toward Candida albicans, the effect of bispecific antibodies (BsAbs) directed against C. albicans and either Fc alpha RI. or Fc gamma RI was evaluated. Control PMNL and in vivo granulocyte colony-stimulating factor (G-CSF)-primed PMNL served as effector cells. A new radiometric killing assay for measuring candidacidal activity was developed to facilitate quantification of PMNL-mediated killing of C. albicans. BsAbs directed to either Fc gamma RI (CD64) or Fc alpha RI (CD89) on human PMNL effectively enhanced both phagocytosis and killing of C. albicans in vitro. Fungicidal activity triggered via Fc gamma RI required in vivo priming with G-CSF, whereas Fc alpha RI-mediated activity was not dependent on this growth factor. Furthermore, PMNL from human Fc gamma RI-transgenic mice effectively phagocytosed and eliminated C. albicans in the presence of BsAbs. These results document the capacity of FcR-directed BsAbs and G-CSF to trigger antifungal immune responses.