ArticlePLoS pathogens2011
Programmed death (PD)-1-deficient mice are extremely sensitive to murine hepatitis virus strain-3 (MHV-3) infection.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Review
- Immune Modulatory Effects of PD-1/PD-L1 in Myasthenia Gravis: Insights From Peripheral Blood Mononuclear Cell Analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Coexisting Lung Cancer and Pulmonary Tuberculosis: A Comprehensive Review From Incidence to Management.Cancer reports (Hoboken, N.J.) · 2025Review
- FGL1 and FGL2: emerging regulators of liver health and disease.Biomarker research · 2024Review
- Natural killer cells and immune-checkpoint inhibitor therapy: Current knowledge and new challenges.Molecular therapy oncolytics · 2022Review
- NK cells require immune checkpoint receptor LILRB4/gp49B to control neurotropic Zika virus infections in mice.JCI insight · 2022Article
- Fibrinogen-like protein 2 deficiency inhibits virus-induced fulminant hepatitis through abrogating inflammatory macrophage activation.World journal of gastroenterology · 2022Article
- Innate lymphoid cells (ILC) in SARS-CoV-2 infection.Molecular aspects of medicine · 2021Review
- The Immune Checkpoint PD-1 in Natural Killer Cells: Expression, Function and Targeting in Tumour Immunotherapy.Cancers · 2020Review
- Human genetic basis of fulminant viral hepatitis.Human genetics · 2020Review
- Depletion of RIPK1 in hepatocytes exacerbates liver damage in fulminant viral hepatitis.Cell death & disease · 2019Article
- Co-stimulatory and co-inhibitory pathways in cancer immunotherapy.Advances in cancer research · 2019Review
- The PD-1/PD-L1 Pathway Affects the Expansion and Function of Cytotoxic CD8Frontiers in immunology · 2019Article
- Soluble fibrinogen-like protein 2 levels in patients with hepatitis B virus-related liver diseases.BMC infectious diseases · 2018Article
- Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD-1 expression on NK cells.Nature immunology · 2018Article
- PD-1 deficiency augments bone marrow failure in a minor-histocompatibility antigen mismatch lymphocyte infusion model.Experimental hematology · 2018Article
- Article
- Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance.Hepatobiliary & pancreatic diseases international : HBPD INT · 2017Review
- PD-1 mediates functional exhaustion of activated NK cells in patients with Kaposi sarcoma.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inhibitory receptor programmed death-1 (PD-1) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however, its precise role in fulminant viral hepatitis (FH) has yet to be described. Here, we investigated the functional mechanisms of PD-1 as related to FH pathogenesis induced by the murine hepatitis virus strain-3 (MHV-3). High levels of PD-1-positive CD4(+), CD8(+) T cells, NK cells and macrophages were observed in liver, spleen, lymph node and thymus tissues following MHV-3 infection. PD-1-deficient mice exhibited significantly higher expression of the effector molecule which initiates fibrinogen deposition, fibrinogen-like protein 2 (FGL2), than did their wild-type (WT) littermates. As a result, more severe tissue damage was produced and mortality rates were higher. Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. Conversely, in vivo blockade of IFN-γ and TNF-α led to efficient inhibition of FGL2 expression, greatly attenuated the development of tissue lesions, and ultimately reduced mortality. Thus, the up-regulation of FGL2 in PD-1-deficient mice was determined to be mediated by IFN-γ and TNF-α. Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy.
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