Linking indirect effects of cytomegalovirus in transplantation to modulation of monocyte innate immune function
| Autor: | Suzanne E. Hickman, Emilia A. H. Vanni, Jay A. Fishman, Rosio Fernandez, Erik R. Abels, Joseph El Khoury, Yiming Yang, Han Chen, Miguel Velazquez-Palafox, Ian J. Taylor, Terry K. Means, Donald M. Coen, Mary E. Piper, Fei Ji, Eric S. Rosenberg, Rebekah J. Lane, Ruslan I. Sadreyev, Jean M. Pesola, Pritha Sen, Bo Li, Adrian R. Wilkie, Liza M. Morsett |
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| Rok vydání: | 2020 |
| Předmět: |
Chemokine
Immunology Congenital cytomegalovirus infection Disease 03 medical and health sciences 0302 clinical medicine immune system diseases medicine Research Articles 030304 developmental biology 0303 health sciences Multidisciplinary Innate immune system biology business.industry Monocyte SciAdv r-articles virus diseases Inflammasome medicine.disease Transplantation surgical procedures operative medicine.anatomical_structure biology.protein Stem cell business Research Article 030215 immunology medicine.drug |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.aax9856 |
| Popis: | CMV-infected monocytes are unable to phagocytose fungal pathogens yet produce inflammation associated with rejection and GVHD. Cytomegalovirus (CMV) is an important cause of morbidity and mortality in the immunocompromised host. In transplant recipients, a variety of clinically important “indirect effects” are attributed to immune modulation by CMV, including increased mortality from fungal disease, allograft dysfunction and rejection in solid organ transplantation, and graft-versus-host-disease in stem cell transplantation. Monocytes, key cellular targets of CMV, are permissive to primary, latent and reactivated CMV infection. Here, pairing unbiased bulk and single cell transcriptomics with functional analyses we demonstrate that human monocytes infected with CMV do not effectively phagocytose fungal pathogens, a functional deficit which occurs with decreased expression of fungal recognition receptors. Simultaneously, CMV-infected monocytes upregulate antiviral, pro-inflammatory chemokine, and inflammasome responses associated with allograft rejection and graft-versus-host disease. Our study demonstrates that CMV modulates both immunosuppressive and immunostimulatory monocyte phenotypes, explaining in part, its paradoxical “indirect effects” in transplantation. These data could provide innate immune targets for the stratification and treatment of CMV disease. |
| Databáze: | OpenAIRE |
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