Persistent viruses evade immune detection by interfering with virus-specific innate and adaptive antiviral immune responses. Fibrinogen-like protein-2 (FGL2) is a potent effector molecule of CD4 CD25 FoxP3 regulatory T cells and exerts its immunosuppressive activity following ligation to its cognate receptor, FcγRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection caused by lymphocytic choriomeningitis virus clone-13 (LCMV cl-13) was assessed in this study. Chronically infected fgl2 mice had increased plasma levels of FGL2, with reduced expression of the maturation markers, CD80, CD86 and MHC-II on macrophages and dendritic cells and impaired production of neutralizing antibody. In contrast, fgl2 mice or fgl2 mice that had been pre-treated with antibodies to FGL2 and FcγRIIB/RIII and then infected with LCMV cl-13 developed a robust CD4 and CD8 antiviral T-cell response, produced high titred neutralizing antibody to LCMV and cleared LCMV. Treatment of mice with established chronic infection with antibodies to FGL2 and FcγRIIB/RIII was shown to rescue the number and functionality of virus-specific CD4 and CD8 T cells with reduced total and virus-specific T-cell expression of programmed cell death protein 1 leading to viral clearance. These results demonstrate an important role for FGL2 in viral immune evasion and provide a rationale to target FGL2 to treat patients with chronic viral infection.
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http://dx.doi.org/10.1111/imm.12897 | DOI Listing |
Shock
November 2024
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Interventional Pulmonology of Zhejiang Province, Wenzhou 325000, Zhejiang Province, China.
Objective: The mechanisms underlying the increased severity of hypertriglyceridemia acute pancreatitis (HTG-AP) remain poorly understood. Fibrinogen-like protein 2 (FGL2) has been identified as a regulator of macrophage activity, mediating immune suppression. This study aims to examine the role of FGL2 in the susceptibility to severe conditions of HTG-AP.
View Article and Find Full Text PDFOncoimmunology
December 2024
Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, China.
Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have emerged as a new therapeutic strategy. In this study, we developed a novel therapeutic polypeptide vaccine targeting the tumor-associated antigen Fibrinogen-Like Protein 2 (FGL2), whose dominant epitope peptide was tandemly linked to the C-terminus of HCMV-IE1mut via a linker.
View Article and Find Full Text PDFJ Transl Med
August 2024
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Background: ERAP2 is an aminopeptidase involved in antigen processing and presentation, and harbor genetic variants linked to several inflammatory diseases such as Inflammatory Bowel Disease (IBD). The lack of an ERAP2 gene homologue in mice has hampered functional studies, and most human studies have focused on cells of hematopoietic origin. Using an IBD biobank as vantage point, this study explores how genetic variation in ERAP2 affects gene expression in human-derived epithelial organoids upon proinflammatory stimulation.
View Article and Find Full Text PDFHeliyon
July 2024
Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Inflammatory bowel disease (IBD) is a refractory disease with immune abnormalities and pathological changes. Intestinal macrophages are considered to be the main factor in establishing and maintaining intestinal homeostasis. The immunoregulatory and anti-inflammatory activity of fibrinogen-like protein 2 (FGL2) can regulate macrophage polarization.
View Article and Find Full Text PDFNat Commun
June 2024
Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
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