Monocytes Latently Infected with Human Cytomegalovirus Evade Neutrophil Killing
| Autor: | Yusuf Aslam, Paul J. Lehner, Kate Roche, Eain A. Murphy, Elizabeth G. Elder, Veronika Romashova, Neda Farahi, Benjamin A. Krishna, John Sinclair, James C Williamson, Edwin R. Chilvers, Alexander J.T. Wood, Emma Poole |
|---|---|
| Přispěvatelé: | Elder, Elizabeth [0000-0003-1615-2642], Krishna, Benjamin Anthony Cates [0000-0003-0919-2961], Williamson, James [0000-0002-2009-189X], Chilvers, Edwin [0000-0002-4230-9677], Lehner, Paul [0000-0001-9383-1054], Sinclair, John [0000-0002-2616-9571], Poole, Emma [0000-0003-3904-6121], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Human cytomegalovirus Myeloid Immunology Human pathogen 02 engineering and technology Article S100A8 03 medical and health sciences Immune system Virology medicine Effector functions lcsh:Science Immune Response Multidisciplinary biology Chemotaxis 021001 nanoscience & nanotechnology medicine.disease 3. Good health 030104 developmental biology medicine.anatomical_structure biology.protein lcsh:Q Molecular Mechanism of Behavior Antibody 0210 nano-technology |
| Zdroj: | iScience iScience, Vol 12, Iss, Pp 13-26 (2019) |
| ISSN: | 2589-0042 |
| Popis: | Summary One site of latency of human cytomegalovirus (HCMV) in vivo is in undifferentiated cells of the myeloid lineage. Although latently infected cells are known to evade host T cell responses by suppression of T cell effector functions, it is not known if they must also evade surveillance by other host immune cells. Here we show that cells latently infected with HCMV can, indeed, be killed by host neutrophils but only in a serum-dependent manner. Specifically, antibodies to the viral latency-associated US28 protein mediate neutrophil killing of latently infected cells. To address this mechanistically, a full proteomic screen was carried out on latently infected monocytes. This showed that latent infection downregulates the neutrophil chemoattractants S100A8/A9, thus suppressing neutrophil recruitment to latently infected cells. The ability of latently infected cells to inhibit neutrophil recruitment represents an immune evasion strategy of this persistent human pathogen, helping to prevent clearance of the latent viral reservoir. Graphical Abstract Highlights • Neutrophils can target HCMV latently infected monocytes for ADCC-mediated killing • Killing of latently infected cells by neutrophils requires high E:T ratios • Latent infection reduces secretion of the neutrophil chemoattractants S100A8/A9 • Decreased S100A8/A9 secretion prevents neutrophil targeting of latently infected cells Molecular Mechanism of Behavior; Immunology; Immune Response; Virology |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|