ISG15 Regulates Peritoneal Macrophages Functionality against Viral Infection

PLoS Pathogens

Klaus-Peter Knobeloch¹  Amelia Nieto²  Mariano Esteban³  Catalina Llompart⁴  Adolfo García-Sastre⁴  Aldo Frau⁵  Alicia García-Culebras⁵  Susana Guerra⁶  Emilio Yángüez⁷  Sylvia Gutierrez-Erlandsson⁸ 

[1] Ciber de Enfermedades Respiratorias, Madrid, Spain;Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America;Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America;Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología CSIC, Madrid, Spain;Department of Preventive Medicine and Public Health, Universidad Autónoma, Madrid, Spain;Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America;Institute of Medical Virology, University of Zurich, Zurich, Switzerland;Institute of Neuropathology, University Freiburg, Freiburg, Germany

关键词: Macrophages;    Phagocytosis;    Apoptosis;    Latex;    Viral transmission;    infection;    Interferons;    Immune response;    Viral replication;   

DOI  :  10.1371/journal.ppat.1003632

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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. ISG15−/− 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.

【 授权许可】

CC BY