Suppressive neutrophils require PIM1 for metabolic fitness and survival during chronic viral infection. Cell Rep 2021 May 25;35(8):109160
Date
05/27/2021Pubmed ID
34038722Pubmed Central ID
PMC8182757DOI
10.1016/j.celrep.2021.109160Scopus ID
2-s2.0-85106489485 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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 TÂ 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.
Author List
Volberding PJ, Xin G, Kasmani MY, Khatun A, Brown AK, Nguyen C, Stancill JS, Martinez E, Corbett JA, Cui WAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Chronic DiseaseHumans
Neutrophils
Proto-Oncogene Proteins c-pim-1
Virus Diseases
