ArticleJCI insight2022
NK cells require immune checkpoint receptor LILRB4/gp49B to control neurotropic Zika virus infections in mice.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases.MedComm · 2026Review
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- CpG oligodeoxynucleotides and pan-serotype inhibitors control neurotropic dengue infection in novel immune competent neonatal mouse model.Emerging microbes & infections · 2025Article
- Peptide-based drugs in immunotherapy: current advances and future prospects.Medical oncology (Northwood, London, England) · 2025Review
- Exploring Mosquito Excreta as an Alternative Sample Type for Improving Arbovirus Surveillance in Australia.Pathogens (Basel, Switzerland) · 2025Article
- Tissue-specific features of innate lymphoid cells in antiviral defense.Cellular & molecular immunology · 2024Review
- The post-stroke young adult brain has limited capacity to re-express the gene expression patterns seen during early postnatal brain development.Brain pathology (Zurich, Switzerland) · 2024Article
- Microglia LILRB4 upregulation reduces brain damage after acute ischemic stroke by limiting CD8Journal of neuroinflammation · 2024Article
- Loss of Mitochondrial Tusc2/Fus1 Triggers a Brain Pro-Inflammatory Microenvironment and Early Spatial Memory Impairment.International journal of molecular sciences · 2024Article
- Review
- Innate lymphoid cells in neuroinflammation.Frontiers in cellular neuroscience · 2024Review
- Effects ofInternational journal of molecular sciences · 2023Article
- Peptide drugs: a new direction in cancer immunotherapy.Cancer biology & medicine · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune cells express an array of inhibitory checkpoint receptors that are upregulated upon activation and limit tissue damage associated with excessive response to pathogens or allergens. Mouse leukocyte immunoglobulin like receptor B4 (LILRB4), also known as glycoprotein 49B (gp49B), is an inhibitory checkpoint receptor constitutively expressed in myeloid cells and upregulated in B cells, T cells, and NK cells upon activation. Here, we report that expression of LILRB4, which binds Zika virus (ZIKV), was increased in microglia and myeloid cells infiltrating the brains of neonatal mice with ZIKV-associated meningoencephalitis. Importantly, while C57BL/6 mice developed transient neurological symptoms but survived infection, mice lacking LILRB4/gp49B (LILRB4 KO) exhibited more severe signs of neurological disease and succumbed to disease. Their brains showed increased cellular infiltration but reduced control of viral burden. The reduced viral clearance was associated with altered NK cell function in the absence of LILRB4/gp49B. In naive animals, this manifested as reduced granzyme B responses to stimulation, but in ZIKV-infected animals, NK cells showed phenotypic changes that suggested altered maturation, diminished glucose consumption, reduced IFN-γ and granzyme B production, and impaired cytotoxicity. Together, our data reveal LILRB4/gp49B as an important regulator of NK cell function during viral infections.
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