ISG15 Regulates Peritoneal Macrophages Functionality against Viral Infection
EntityUAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología
PublisherPublic Library of Science
10.1371/journal.ppat.1003632PloS Pathogens 9.10 (2013): e1003632
ISSN1553-7366 (print); 1553-7374 (online)
Funded byThis work was supported by grants from the Spanish Ministry of Health FIS2011-00127, Comunidad de Madrid UAM-CM-CCG10-4911 and UAM-Banco de Santander to SG. This work was also partly supported by NIAID grant U19AI083025 and by CRIP (Center for Research on Influenza Pathogenesis, HHSN266200700010C), a NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS) to AGS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
ProjectGobierno de España. FIS2011-00127
SubjectsViral infection; Antiviral; Medicina
Rights© 2013 Yángüez et al.
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Upon viral infection, the production of type I interferon (IFN) and the subsequent upregulation of IFN stimulated genes (ISGs) generate an antiviral state with an important role in the activation of innate and adaptive host immune responses. The ubiquitin-like protein (UBL) ISG15 is a critical IFN-induced antiviral molecule that protects against several viral infections, but the mechanism by which ISG15 exerts its antiviral function is not completely understood. Here, we report that ISG15 plays an important role in the regulation of macrophage responses. ISG152/2 macrophages display reduced activation, phagocytic capacity and programmed cell death activation in response to vaccinia virus (VACV) infection. Moreover, peritoneal macrophages from mice lacking ISG15 are neither able to phagocyte infected cells nor to block viral infection in co-culture experiments with VACV-infected murine embryonic fibroblast (MEFs). This phenotype is independent of cytokine production and secretion, but clearly correlates with impaired activation of the protein kinase AKT in ISG15 knock-out (KO) macrophages. Altogether, these results indicate an essential role of ISG15 in the cellular immune antiviral response and point out that a better understanding of the antiviral responses triggered by ISG15 may lead to the development of therapies against important human pathogens
Google Scholar:Yángüez, Emilio - García-Culebras, Alicia - Frau, Aldo - Llompart, Catalina - Knobeloch, Klaus Peter - Gutiérrez-Erlandsson, Sylvia - García-Sastre, Adolfo - Esteban, Mariano - Nieto, Amelia
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