Protective role of Toll-like Receptor 3-induced type I interferon in murine coronavirus infection of macrophages
Open accessAbstract
Toll-like Receptors (TLRs) sense viral infections and induce production of type I interferons (IFNs), other cytokines, and chemokines. Viral recognition by TLRs and other pattern recognition receptors (PRRs) has been proven to be cell-type specific. Triggering of TLRs with selected ligands can be beneficial against some viral infections. Macrophages are antigen-presenting cells that express TLRs and have a key role in the innate and adaptive immunity against viruses. Coronaviruses (CoVs) are single-stranded, positive-sense RNA viruses that cause acute and chronic infections and can productively infect macrophages. Investigation of the interplay between CoVs and PRRs is in its infancy. We assessed the effect of triggering TLR2, TLR3, TLR4, and TLR7 with selected ligands on the susceptibility of the J774A.1 macrophage cell line to infection with murine coronavirus (mouse hepatitis virus, [MHV]). Stimulation of TLR2, TLR4, or TLR7 did not affect MHV production. In contrast, pre-stimulation of TLR3 with polyinosinic-polycytidylic acid (poly I:C) hindered MHV infection through induction of IFN-β in macrophages. We demonstrate that activation of TLR3 with the synthetic ligand poly I:C mediates antiviral immunity that diminishes (MHV-A59) or suppresses (MHV-JHM, MHV-3) virus production in macrophages.
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The pattern recognition receptors involved in recognizing SARS-CoV-2 are not yet directly determined; based on other coronaviruses, the most likely candidates are endosomal TLR3 and TLR7 or cytosolic RIG-I and MDA5.
“Similarly, the pattern recognition receptors (PRRs) involved in recognizing SARS-CoV-2 are not yet directly determined. Based on findings from other coronaviruses, the most likely candidates are Toll-like receptors 3 (TLR3) and TLR7 in the endosome (Mazaleuskaya et al., 2012) or the cytosolic sensors retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) (Sa R”
From COVID-19 and the human innate immune system (2021) · cites this paper as Mazaleuskaya et al., 2012
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- Authors
- Mazaleuskaya, L., Veltrop, R., Ikpeze, N., Martin-Garcia, J., & Navas-Martin, S.
- Affiliations
- Drexel University (US)
- Department of Microbiology and Immunology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA 19102, USA
- Venue
- Viruses
- Publisher
- MDPI AG
- Published
- 2012-05-24
- Volume
- 4
- Issue
- 5
- Pages
- 901-923
- ISSN
- 1999-4915 (ISSN-L)
- PMC
- PMC3386628
- OpenAlex
- W2078889234
- Cited by
- 89
- References
- 55
- Citations by year
- 2025: 3 · 2024: 8 · 2023: 9 · 2022: 12 · 2021: 20 · 2020: 9 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 1
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Viruses (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Drexel University
- College of Medicine, Drexel University
- National Institute of Allergy and Infectious Diseases (R21AI088423, AI-088423)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-089314, R21DK089314)
- National Institute of Neurological Disorders and Stroke (R03NS061179, NS061179, NS-065727, R01NS065727)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- TLR3, type I interferon, interferon-beta, mouse hepatitis virus, macrophages, polyinosinic-polycytidylic acid, antiviral immunity, pattern recognition receptors, TLR2, TLR4, TLR7, J774A.1 cells, viral replication inhibition
- MeSH terms
- Animals, Cell Line, Murine hepatitis virus, Interferon Type I, Macrophages, Poly I-C, Coronavirus Infections, Toll-Like Receptor 3, Mice
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