FC GAMMA RECEPTOR ACTIVATION IN MICROGLIA IN RESPONSE TO CRYPTOCOCCUS

Cryptococcus neoformans is an encapsulated fungal pathogen that is remarkable for its ability to cause central nervous system (CNS) infections especially in patients with AIDS. Increasing evidence suggests that microglia play a central role in the host response in cryptococcal meningoencephalitis. However, the mechanism by which microglia regulate the inflammatory process is poorly understood. We studied the microglial Fc receptor activation in response to C. neoformans-mAb challenge and showed that FcγR activation is a powerful means of microglial gene induction. We also showed that distinct FcR subtypes and signaling pathways are involved in phagocytosis and chemokine expression. Our results thus indicate that antibody-deficiency can lead to inadequate phagocyte activation and insufficient inflammatory cell recruitment to the CNS. As the biological activity of C. neoformans immune complex in microglia was attributable to the activation of microglial FcR, our study has implications beyond cryptococcal infection in which antibody (natural or administered) can encounter antigens within the CNS.