Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection
SARS-CoV-2, a member of the coronavirus family, is the causative agent of the COVID-19 pandemic. Currently, there is still an urgent need in developing an efficient therapeutic intervention. In this study, we aimed at evaluating the therapeutic effect of a single intranasal treatment of the TLR3/MDA...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/2/189 |
| _version_ | 1797476041251356672 |
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| author | Hadas Tamir Sharon Melamed Noam Erez Boaz Politi Yfat Yahalom-Ronen Hagit Achdout Shlomi Lazar Hila Gutman Roy Avraham Shay Weiss Nir Paran Tomer Israely |
| author_facet | Hadas Tamir Sharon Melamed Noam Erez Boaz Politi Yfat Yahalom-Ronen Hagit Achdout Shlomi Lazar Hila Gutman Roy Avraham Shay Weiss Nir Paran Tomer Israely |
| author_sort | Hadas Tamir |
| collection | DOAJ |
| description | SARS-CoV-2, a member of the coronavirus family, is the causative agent of the COVID-19 pandemic. Currently, there is still an urgent need in developing an efficient therapeutic intervention. In this study, we aimed at evaluating the therapeutic effect of a single intranasal treatment of the TLR3/MDA5 synthetic agonist Poly(I:C) against a lethal dose of SARS-CoV-2 in K18-hACE2 transgenic mice. We demonstrate here that early Poly(I:C) treatment acts synergistically with SARS-CoV-2 to induce an intense, immediate and transient upregulation of innate immunity-related genes in lungs. This effect is accompanied by viral load reduction, lung and brain cytokine storms prevention and increased levels of macrophages and NK cells, resulting in 83% mice survival, concomitantly with long-term immunization. Thus, priming the lung innate immunity by Poly(I:C) or alike may provide an immediate, efficient and safe protective measure against SARS-CoV-2 infection. |
| first_indexed | 2024-03-09T20:52:20Z |
| format | Article |
| id | doaj.art-22200493a15f45b591f98fb1cb0667bb |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T20:52:20Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-22200493a15f45b591f98fb1cb0667bb2023-11-23T22:29:00ZengMDPI AGViruses1999-49152022-01-0114218910.3390/v14020189Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 InfectionHadas Tamir0Sharon Melamed1Noam Erez2Boaz Politi3Yfat Yahalom-Ronen4Hagit Achdout5Shlomi Lazar6Hila Gutman7Roy Avraham8Shay Weiss9Nir Paran10Tomer Israely11Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelDepartment of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, IsraelSARS-CoV-2, a member of the coronavirus family, is the causative agent of the COVID-19 pandemic. Currently, there is still an urgent need in developing an efficient therapeutic intervention. In this study, we aimed at evaluating the therapeutic effect of a single intranasal treatment of the TLR3/MDA5 synthetic agonist Poly(I:C) against a lethal dose of SARS-CoV-2 in K18-hACE2 transgenic mice. We demonstrate here that early Poly(I:C) treatment acts synergistically with SARS-CoV-2 to induce an intense, immediate and transient upregulation of innate immunity-related genes in lungs. This effect is accompanied by viral load reduction, lung and brain cytokine storms prevention and increased levels of macrophages and NK cells, resulting in 83% mice survival, concomitantly with long-term immunization. Thus, priming the lung innate immunity by Poly(I:C) or alike may provide an immediate, efficient and safe protective measure against SARS-CoV-2 infection.https://www.mdpi.com/1999-4915/14/2/189SARS-CoV-2COVID-19hACE2-K18 transgenic miceTLR3Poly(I:C)innate immune response |
| spellingShingle | Hadas Tamir Sharon Melamed Noam Erez Boaz Politi Yfat Yahalom-Ronen Hagit Achdout Shlomi Lazar Hila Gutman Roy Avraham Shay Weiss Nir Paran Tomer Israely Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection Viruses SARS-CoV-2 COVID-19 hACE2-K18 transgenic mice TLR3 Poly(I:C) innate immune response |
| title | Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection |
| title_full | Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection |
| title_fullStr | Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection |
| title_full_unstemmed | Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection |
| title_short | Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection |
| title_sort | induction of innate immune response by tlr3 agonist protects mice against sars cov 2 infection |
| topic | SARS-CoV-2 COVID-19 hACE2-K18 transgenic mice TLR3 Poly(I:C) innate immune response |
| url | https://www.mdpi.com/1999-4915/14/2/189 |
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