Effective phagocytosis and killing of Candida albicans via targeting Fc gamma RI (CD64) or Fc alpha RI (CD89) on neutrophils

Invasive fungal infections are an increasing problem for immunocompromised patients. As an approach to improve targeting of polymorphonuclear leukocyt es (PMNL) toward Candida albicans, the effect of bispecific antibodies (BsA bs) 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 ass ay for measuring candidacidal activity was developed to facilitate quantifi cation 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 b oth phagocytosis and killing of C. albicans in vitro. Fungicidal activity t riggered via Fc gamma RI required in vivo priming with G-CSF, whereas Fc al pha RI-mediated activity was not dependent on this growth factor. Furthermo re, PMNL from human Fc gamma RI-transgenic mice effectively phagocytosed an d eliminated C. albicans in the presence of BsAbs. These results document t he capacity of FcR-directed BsAbs and G-CSF to trigger antifungal immune re sponses.