The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection
Abstract Background The conventional means of controlling the recurring pandemics of Type A Influenza Virus (IAV) infections remain challenging primarily because of its high mutability and increasing drug resistance. As an alternative to control IAV infections, the prophylactic use of cytokines to d...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Gut Pathogens |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13099-023-00578-5 |
| _version_ | 1827770552220123136 |
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| author | Sandeep Yadav Aparna Varma Aparna Odayil Muralidharan Sucharita Bhowmick Samiran Mondal Amirul Islam Mallick |
| author_facet | Sandeep Yadav Aparna Varma Aparna Odayil Muralidharan Sucharita Bhowmick Samiran Mondal Amirul Islam Mallick |
| author_sort | Sandeep Yadav |
| collection | DOAJ |
| description | Abstract Background The conventional means of controlling the recurring pandemics of Type A Influenza Virus (IAV) infections remain challenging primarily because of its high mutability and increasing drug resistance. As an alternative to control IAV infections, the prophylactic use of cytokines to drive immune activation of multiple antiviral host factors has been progressively recognized. Among them, Type III Interferons (IFNs) exhibit a pivotal role in inducing potent antiviral host responses by upregulating the expression of several antiviral genes, including the Interferon-Stimulated Genes (ISGs) that specifically target the virus replication machinery. To harness the immuno-adjunctive potential, we examined whether pre-treatment of IFNλ3, a Type III IFN, can activate antiviral host responses against IAV infections. Methods In the present study, we bioengineered a food-grade lactic acid-producing bacteria (LAB), Lactococcus lactis (L. lactis), to express and secrete functional murine IFNλ3 (MuIFNλ3) protein in the extracellular milieu. To test the immune-protective potential of MuIFNλ3 secreted by recombinant L. lactis (rL. lactis), we used murine B16F10 cells as an in vitro model while mice (BALB/c) were used for in vivo studies. Results Our study demonstrated that priming with MuIFNλ3 secreted by rL. lactis could upregulate the expression of several antiviral genes, including Interferon Regulatory Factors (IRFs) and ISGs, without exacerbated pulmonary or intestinal inflammatory responses. Moreover, we also showed that pre-treatment of B16F10 cells with MuIFNλ3 can confer marked immune protection against mice-adapted influenza virus, A/PR/8/1934 (H1N1) infection. Conclusion Since the primary target for IAV infections is the upper respiratory and gastrointestinal tract, immune activation without affecting the tissue homeostasis suggests the immune-adjunctive potential of IFNλ3 against IAV infections. |
| first_indexed | 2024-03-11T12:41:12Z |
| format | Article |
| id | doaj.art-e655a2c16b1f464683fbefb322d99fec |
| institution | Directory Open Access Journal |
| issn | 1757-4749 |
| language | English |
| last_indexed | 2024-03-11T12:41:12Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Gut Pathogens |
| spelling | doaj.art-e655a2c16b1f464683fbefb322d99fec2023-11-05T12:19:26ZengBMCGut Pathogens1757-47492023-10-0115111710.1186/s13099-023-00578-5The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infectionSandeep Yadav0Aparna Varma1Aparna Odayil Muralidharan2Sucharita Bhowmick3Samiran Mondal4Amirul Islam Mallick5Department of Biological Sciences, Indian Institute of Science Education and Research KolkataDepartment of Biological Sciences, Indian Institute of Science Education and Research KolkataDepartment of Biological Sciences, Indian Institute of Science Education and Research KolkataDepartment of Biological Sciences, Indian Institute of Science Education and Research KolkataDepartment of Veterinary Pathology, West Bengal University of Animal and Fishery SciencesDepartment of Biological Sciences, Indian Institute of Science Education and Research KolkataAbstract Background The conventional means of controlling the recurring pandemics of Type A Influenza Virus (IAV) infections remain challenging primarily because of its high mutability and increasing drug resistance. As an alternative to control IAV infections, the prophylactic use of cytokines to drive immune activation of multiple antiviral host factors has been progressively recognized. Among them, Type III Interferons (IFNs) exhibit a pivotal role in inducing potent antiviral host responses by upregulating the expression of several antiviral genes, including the Interferon-Stimulated Genes (ISGs) that specifically target the virus replication machinery. To harness the immuno-adjunctive potential, we examined whether pre-treatment of IFNλ3, a Type III IFN, can activate antiviral host responses against IAV infections. Methods In the present study, we bioengineered a food-grade lactic acid-producing bacteria (LAB), Lactococcus lactis (L. lactis), to express and secrete functional murine IFNλ3 (MuIFNλ3) protein in the extracellular milieu. To test the immune-protective potential of MuIFNλ3 secreted by recombinant L. lactis (rL. lactis), we used murine B16F10 cells as an in vitro model while mice (BALB/c) were used for in vivo studies. Results Our study demonstrated that priming with MuIFNλ3 secreted by rL. lactis could upregulate the expression of several antiviral genes, including Interferon Regulatory Factors (IRFs) and ISGs, without exacerbated pulmonary or intestinal inflammatory responses. Moreover, we also showed that pre-treatment of B16F10 cells with MuIFNλ3 can confer marked immune protection against mice-adapted influenza virus, A/PR/8/1934 (H1N1) infection. Conclusion Since the primary target for IAV infections is the upper respiratory and gastrointestinal tract, immune activation without affecting the tissue homeostasis suggests the immune-adjunctive potential of IFNλ3 against IAV infections.https://doi.org/10.1186/s13099-023-00578-5Murine IFNλ3 (MuIFNλ3)Lactococcus lactis (L. lactis)Type A Influenza Virus (IAV)Immune protection |
| spellingShingle | Sandeep Yadav Aparna Varma Aparna Odayil Muralidharan Sucharita Bhowmick Samiran Mondal Amirul Islam Mallick The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection Gut Pathogens Murine IFNλ3 (MuIFNλ3) Lactococcus lactis (L. lactis) Type A Influenza Virus (IAV) Immune protection |
| title | The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection |
| title_full | The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection |
| title_fullStr | The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection |
| title_full_unstemmed | The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection |
| title_short | The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection |
| title_sort | immune adjunctive potential of recombinant lab vector expressing murine ifnλ3 muifnλ3 against type a influenza virus iav infection |
| topic | Murine IFNλ3 (MuIFNλ3) Lactococcus lactis (L. lactis) Type A Influenza Virus (IAV) Immune protection |
| url | https://doi.org/10.1186/s13099-023-00578-5 |
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