Suppression of adaptive NK cell expansion by macrophage-mediated phagocytosis inhibited by 2B4-CD48
Rui Li,
Cristian Camilo Galindo,
Dominique Davidson,
Huaijian Guo,
Ming-Chao Zhong,
Jin Qian,
Bin Li,
Zsolt Ruzsics,
Colleen M. Lau,
Timothy E. O'Sullivan,
Silvia M. Vidal,
Joseph C. Sun,
André Veillette
Affiliations
Rui Li
Laboratory of Molecular Oncology, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada; Department of Medicine, McGill University, Montréal, QC H3G 1Y6, Canada
Cristian Camilo Galindo
Laboratory of Molecular Oncology, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada; Department of Medicine, McGill University, Montréal, QC H3G 1Y6, Canada
Dominique Davidson
Laboratory of Molecular Oncology, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada
Huaijian Guo
Laboratory of Molecular Oncology, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada; Department of Medicine, McGill University, Montréal, QC H3G 1Y6, Canada
Ming-Chao Zhong
Laboratory of Molecular Oncology, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada
Jin Qian
Laboratory of Molecular Oncology, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada
Bin Li
Laboratory of Molecular Oncology, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada; Molecular Biology Program, University of Montréal, Montréal, QC H3T 1J4, Canada
Zsolt Ruzsics
Institute of Virology, University Medical Center, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
Colleen M. Lau
Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
Timothy E. O'Sullivan
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Silvia M. Vidal
Department of Human Genetics, McGill University, Montréal, QC H3A 0C7, Canada; Dahdaleh Institute of Genomic Medicine, McGill University, Montréal, QC H3A 0G1, Canada
Joseph C. Sun
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065, USA
André Veillette
Laboratory of Molecular Oncology, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada; Department of Medicine, McGill University, Montréal, QC H3G 1Y6, Canada; Molecular Biology Program, University of Montréal, Montréal, QC H3T 1J4, Canada; Corresponding author
Summary: Infection of mice by mouse cytomegalovirus (MCMV) triggers activation and expansion of Ly49H+ natural killer (NK) cells, which are virus specific and considered to be “adaptive” or “memory” NK cells. Here, we find that signaling lymphocytic activation molecule family receptors (SFRs), a group of hematopoietic cell-restricted receptors, are essential for the expansion of Ly49H+ NK cells after MCMV infection. This activity is largely mediated by CD48, an SFR broadly expressed on NK cells and displaying augmented expression after MCMV infection. It is also dependent on the CD48 counter-receptor, 2B4, expressed on host macrophages. The 2B4-CD48 axis promotes expansion of Ly49H+ NK cells by repressing their phagocytosis by virus-activated macrophages through inhibition of the pro-phagocytic integrin lymphocyte function-associated antigen-1 (LFA-1) on macrophages. These data identify key roles of macrophages and the 2B4-CD48 pathway in controlling the expansion of adaptive NK cells following MCMV infection. Stimulation of the 2B4-CD48 axis may be helpful in enhancing adaptive NK cell responses for therapeutic purposes.
