RT Journal Article
SR Electronic
T1 Increasing phagocytosis of microglia through targeting CD33 with liposomes displaying glycan ligands
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.08.443135
DO 10.1101/2021.05.08.443135
A1 Abhishek Bhattacherjee
A1 Gour Chand Daskhan
A1 Arjun Bains
A1 Adrianne E. S. Watson
A1 Ghazaleh Eskandari-Sedighi
A1 Chris D. St. Laurent
A1 Anastassia Voronova
A1 Matthew S. Macauley
YR 2021
UL http://biorxiv.org/content/early/2021/05/09/2021.05.08.443135.abstract
AB CD33 is an immunomodulatory receptor expressed on microglia and genetically linked to Alzheimer’s disease (AD) susceptibility. While antibodies targeting CD33 have entered clinical trials to treat neurodegeneration, it is unknown whether the glycan-binding properties of CD33 can be exploited to modulate microglia. Here, we use liposomes that multivalently display glycan ligands of CD33 (CD33L liposomes) to engage CD33. We find that CD33L liposomes increase phagocytosis of cultured monocytic cells and microglia in a CD33-dependent manner. Enhanced phagocytosis strongly correlates with loss of CD33 from the cell surface and internalization of liposomes. Increased phagocytosis by treatment with CD33L liposomes is dependent on a key intracellular signaling motif on CD33 as well as the glycan-binding ability of CD33. These effects are specific to trans engagement of CD33 by CD33L liposomes, as cis engagement through insertion of lipid-linked CD33L into cells produces the opposite effect on phagocytosis. Moreover, intracerebroventricular injection of CD33L liposomes in mice enhances phagocytosis of microglia in a CD33-dependent manner. These results demonstrate that multivalent engagement of CD33 with glycan ligands can modulate microglial cell function.Competing Interest StatementThe authors have declared no competing interest.