학술논문
Suppressive neutrophils require PIM1 for metabolic fitness and survival during chronic viral infection.
Document Type
Academic Journal
Author
Volberding PJ; Versiti Blood Research Institute, 8727 West Watertown Plank Rd., Milwaukee, WI 53213, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 West Watertown Plank Rd., Milwaukee, WI 53226, USA.; Xin G; Versiti Blood Research Institute, 8727 West Watertown Plank Rd., Milwaukee, WI 53213, USA; Department of Microbial Infection and Immunity, The Ohio State University College of Medicine, 370 W. 9(th) Ave., Columbus, OH 43210, USA; Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, The Ohio State University, 460 W. 10(th) Ave., Columbus, OH 43210, USA.; Kasmani MY; Versiti Blood Research Institute, 8727 West Watertown Plank Rd., Milwaukee, WI 53213, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 West Watertown Plank Rd., Milwaukee, WI 53226, USA.; Khatun A; Versiti Blood Research Institute, 8727 West Watertown Plank Rd., Milwaukee, WI 53213, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 West Watertown Plank Rd., Milwaukee, WI 53226, USA.; Brown AK; Versiti Blood Research Institute, 8727 West Watertown Plank Rd., Milwaukee, WI 53213, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 West Watertown Plank Rd., Milwaukee, WI 53226, USA.; Nguyen C; Versiti Blood Research Institute, 8727 West Watertown Plank Rd., Milwaukee, WI 53213, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 West Watertown Plank Rd., Milwaukee, WI 53226, USA.; Stancill JS; Department of Biochemistry, Medical College of Wisconsin, 8701 West Watertown Plank Rd., Milwaukee, WI 53226, USA.; Martinez E; Versiti Blood Research Institute, 8727 West Watertown Plank Rd., Milwaukee, WI 53213, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 West Watertown Plank Rd., Milwaukee, WI 53226, USA.; Corbett JA; Department of Biochemistry, Medical College of Wisconsin, 8701 West Watertown Plank Rd., Milwaukee, WI 53226, USA.; Cui W; Versiti Blood Research Institute, 8727 West Watertown Plank Rd., Milwaukee, WI 53213, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 West Watertown Plank Rd., Milwaukee, WI 53226, USA. Electronic address: wecui@mcw.edu.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
Subject
Language
English
Abstract
The immune response to a chronic viral infection is uniquely tailored to balance viral control and immunopathology. The role of myeloid cells in shaping the response to chronic viral infection, however, is poorly understood. We perform single-cell RNA sequencing of myeloid cells during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection to address this question. Our analysis identifies a cluster of suppressive neutrophils that is enriched in chronic infection. Furthermore, suppressive neutrophils highly express the gene encoding Proviral integration site for Moloney murine leukemia virus-1 (PIM1), a kinase known to promote mitochondrial fitness and cell survival. Pharmacological inhibition of PIM1 selectively diminishes suppressive neutrophil-mediated immunosuppression without affecting the function of monocytic myeloid-derived suppressor cells (M-MDSCs). Decreased accumulation of suppressive neutrophils leads to increased CD8 T cell function and viral control. Mechanistically, PIM kinase activity is required for maintaining fused mitochondrial networks in suppressive neutrophils, but not in M-MDSCs, and loss of PIM kinase function causes increased suppressive neutrophil apoptosis.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)