Focused ultrasound immunomodulation on mononuclear phagocytes in the brain

Abstract

Focused ultrasound (FUS)-mediated blood–brain barrier opening is an attractive method of treating neurological diseases, such as glioblastoma (GBM) and Alzheimer’s disease (AD). As an established drug delivery approach, FUS has also been associated with the stimulation of neuro-inflammation, including the morphological activation of resident microglia. Here we report FUS immunomodulation effects may also include the enhanced recruitment and activation of other mononuclear phagocytes in murine models of GBM (GL261) and AD (APP/PS1dE9) in tests with or without monoclonal antibody-based passive immunotherapy. Immunoprofiling via flow cytometry and immunofluorescent staining were performed in the harvested brains. In the GBM model, our results demonstrated that FUS enhanced antigen presentation behaviors of tumor-associated macrophages without affecting the microglia. FUS also reprogrammed the macrophages locally towards the anti-cancer phenotype. In the AD model, plaque-associated Ly6G+ phagocytes were only present in FUS-treated areas, while microglia activation was found in both antibody-treated groups. Taken together, our results offer new evidence in FUS immunomodulation on the myeloid compartment of the brains in GBM and AD-like mouse models.