[en] The interaction of neutrophils with T cells has been the subject of debate and controversies. Previous studies have suggested that neutrophils may suppress or activate T cells. Despite these studies, the interaction between neutrophils and T cells has remained a largely unexplored field. Here, based on our RNA sequencing (RNA-seq) analysis, we found that neutrophils have differential transcriptional and functional profiling depending on the CD4 T-cell count of the HIV-infected individual. In particular, we identified that neutrophils in healthy individuals express surface Galectin-9 (Gal-9), which is down-regulated upon activation, and is consistently down-regulated in HIV-infected individuals. However, down-regulation of Gal-9 was associated with CD4 T-cell count of patients. Unstimulated neutrophils express high levels of surface Gal-9 that is bound to CD44, and, upon stimulation, neutrophils depalmitoylate CD44 and induce its movement out of the lipid raft. This process causes the release of Gal-9 from the surface of neutrophils. In addition, we found that neutrophil-derived exogenous Gal-9 binds to cell surface CD44 on T cells, which promotes LCK activation and subsequently enhances T-cell activation. Furthermore, this process was regulated by glycolysis and can be inhibited by interleukin (IL)-10. Together, our data reveal a novel mechanism of Gal-9 shedding from the surface of neutrophils. This could explain elevated plasma Gal-9 levels in HIV-infected individuals as an underlying mechanism of the well-characterized chronic immune activation in HIV infection. This study provides a novel role for the Gal-9 shedding from neutrophils. We anticipate that our results will spark renewed investigation into the role of neutrophils in T-cell activation in other acute and chronic conditions, as well as improved strategies for modulating Gal-9 shedding.
Disciplines :
Immunology & infectious disease
Author, co-author :
Dunsmore, Garett ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Physiologie générale et des systèmes ; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Rosero, Eliana Perez ; School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Shahbaz, Shima; School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Santer, Deanna M ; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. ; Li Ka Shing Institute of Virology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Jovel, Juan; School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Lacy, Paige ; Department of Medicine, Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Houston, Stan; Department of Medicine, Division of Infectious Disease, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Elahi, Shokrollah ; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. ; School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. ; Li Ka Shing Institute of Virology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. ; Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Language :
English
Title :
Neutrophils promote T-cell activation through the regulated release of CD44-bound Galectin-9 from the cell surface during HIV infection.
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