Neutrophil Fc gamma RI as target for immunotherapy of invasive candidiasis

Invasive candidiasis represents a life-threatening disease for immunocompro mised patients. This study focused on new immunotherapeutic approaches for systemic Candida albicans infections in a human Fc gamma RI-transgenic mous e model. Fc gamma RI (CD64) is a potent immunoactivating receptor on phagoc ytic and dendritic cells. In vivo targeting of C. albicans toward neutrophi l-Fc gamma RI by bispecific Abs and G-CSF effectively protected Fc gamma RI -transgenic mice from lethal candidiasis. Nontransgenic mice were not prote cted, and treatment with bispecific Ab or G-CSF alone did not reduce mortal ity. Furthermore, infected Fc gamma RI-transgenic mice developed high titer s of anti-C. albicans IgG, and survival was extended on secondary infection without further treatment. These findings document the capacity of Fc gamm a RI to initiate potent anti-C. albicans immunity and support the developme nt of Fc gamma RI-directed immunotherapy of invasive fungal disease.