Pneumococcal capsular polysaccharide-specific IgA triggers efficient neutrophil effector functions via FcalphaRI (CD89).

Specific anti-capsular polysaccharide IgG is believed to be important for protection against infection by Streptococcus pneumoniae. Significant IgA responses have been observed after vaccination with pneumococcal vaccines, but the role of this isotype in anti-pneumococcal host defense is unclear. Here, it is shown that purified serum IgA specific for pneumococcal capsular polysaccharides can initiate efficient cellular effector functions, such as phagocytosis, via interaction with the myeloid IgA receptor, FcalphaRI (CD89). The efficiency of FcalphaR-triggered granulocyte effector functions was comparable to that of FcgammaRIIa (CD32), as shown in experiments with bispecific antibodies. These results support a role for polysaccharide-specific IgA in antipneumococcal cellular effector function and suggest that FcalphaRI represents an important leukocyte receptor for immunity against S. pneumoniae.

Effective phagocytosis and killing of Candida albicans via targeting FcgammaRI (CD64) or FcalphaRI (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 FcalphaRI or FcgammaRI 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 FcgammaRI (CD64) or FcalphaRI (CD89) on human PMNL effectively enhanced both phagocytosis and killing of C. albicans in vitro. Fungicidal activity triggered via FcgammaRI required in vivo priming with G-CSF, whereas FcalphaRI-mediated activity was not dependent on this growth factor. Furthermore, PMNL from human FcgammaRI-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.