Repression of phagocytosis by human CD33 is not conserved with mouse CD33

Abhishek Bhattacherjee; Emily Rodrigues; Jaesoo Jung; Matthew Luzentales-Simpson; Jhon R Enterina; Danny Galleguillos; Chris D St Laurent; Maryam Nakhaei-Nejad; Felix F Fuchsberger; Laura Streith; Qian Wang; Norihito Kawasaki; Shiteng Duan; Arjun Bains; James C Paulson; Christoph Rademacher; Fabrizio Giuliani; Simonetta Sipione; Matthew S Macauley

doi:10.1038/s42003-019-0698-6

Repression of phagocytosis by human CD33 is not conserved with mouse CD33

Commun Biol. 2019 Dec 3:2:450. doi: 10.1038/s42003-019-0698-6. eCollection 2019.

Authors

Abhishek Bhattacherjee¹, Emily Rodrigues¹, Jaesoo Jung¹, Matthew Luzentales-Simpson², Jhon R Enterina², Danny Galleguillos³, Chris D St Laurent¹, Maryam Nakhaei-Nejad⁴, Felix F Fuchsberger⁵, Laura Streith², Qian Wang³, Norihito Kawasaki⁶, Shiteng Duan⁶, Arjun Bains¹, James C Paulson⁶, Christoph Rademacher⁵, Fabrizio Giuliani⁴, Simonetta Sipione³, Matthew S Macauley^{1

2}

Affiliations

¹ 1Department of Chemistry, University of Alberta, Alberta, Canada.
² 2Department of Medical Microbiology and Immunology, University of Alberta, Alberta, Canada.
³ 3Department of Pharmacology, University of Alberta, Alberta, Canada.
⁴ 4Department of Medicine, University of Alberta, Alberta, Canada.
⁵ 5Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
⁶ 6Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037 USA.

Abstract

CD33 is an immunomodulatory receptor linked to Alzheimer's disease (AD) susceptibility via regulation of phagocytosis in microglia. Divergent features between human CD33 (hCD33) and murine CD33 (mCD33) include a unique transmembrane lysine in mCD33 and cytoplasmic tyrosine in hCD33. The functional consequences of these differences in restraining phagocytosis remains poorly understood. Using a new αmCD33 monoclonal antibody, we show that mCD33 is expressed at high levels on neutrophils and low levels on microglia. Notably, cell surface expression of mCD33 is entirely dependent on Dap12 due to an interaction with the transmembrane lysine in mCD33. In RAW264.7 cultured macrophages, BV-2 cultured microglia, primary neonatal and adult microglia, uptake of cargo - including aggregated Aβ_1-42 - is not altered upon genetic ablation of mCD33. Alternatively, deletion of hCD33 in monocytic cell lines increased cargo uptake. Moreover, transgenic mice expressing hCD33 in the microglial cell lineage showed repressed cargo uptake in primary microglia. Therefore, mCD33 and hCD33 have divergent roles in regulating phagocytosis, highlighting the importance of studying hCD33 in AD susceptibility.

Keywords: Microglia; Neuroimmunology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Abstract

Publication types

Grants and funding