<i>Lactococcus lactis</i> Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune Repertoire
Inflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation comprised of Crohn’s disease and ulcerative colitis. Centers for Disease Control and Prevention report that 1.3% of the population of the United States (approximately 3 million people) were affected by the disease in...
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MDPI AG
2021-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/9/1098 |
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| author | Ananta Prasad Arukha Christian Furlan Freguia Meerambika Mishra Jyoti K. Jha Subhashinie Kariyawasam Neil A. Fanger Ellen M. Zimmermann Gary R. Fanger Bikash Sahay |
| author_facet | Ananta Prasad Arukha Christian Furlan Freguia Meerambika Mishra Jyoti K. Jha Subhashinie Kariyawasam Neil A. Fanger Ellen M. Zimmermann Gary R. Fanger Bikash Sahay |
| author_sort | Ananta Prasad Arukha |
| collection | DOAJ |
| description | Inflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation comprised of Crohn’s disease and ulcerative colitis. Centers for Disease Control and Prevention report that 1.3% of the population of the United States (approximately 3 million people) were affected by the disease in 2015, and the number keeps increasing over time. IBD has a multifactorial etiology, from genetic to environmental factors. Most of the IBD treatments revolve around disease management, by reducing the inflammatory signals. We previously identified the surface layer protein A (SlpA) of <i>Lactobacillus acidophilus</i> that possesses anti-inflammatory properties to mitigate murine colitis. Herein, we expressed SlpA in a clinically relevant, food-grade <i>Lactococcus lactis</i> to further investigate and characterize the protective mechanisms of the actions of SlpA. Oral administration of SlpA-expressing <i>L. lactis</i> (R110) mitigated the symptoms of murine colitis. Oral delivery of R110 resulted in a higher expression of IL-27 by myeloid cells, with a synchronous increase in IL-10 and cMAF in T cells. Consistent with murine studies, human dendritic cells exposed to R110 showed exquisite differential gene regulation, including IL-27 transcription, suggesting a shared mechanism between the two species, hence positioning R110 as potentially effective at treating colitis in humans. |
| first_indexed | 2024-03-10T07:53:24Z |
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| institution | Directory Open Access Journal |
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| last_indexed | 2024-03-10T07:53:24Z |
| publishDate | 2021-08-01 |
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| series | Biomedicines |
| spelling | doaj.art-87ebad7bd9a942dfa799de5cc4e70af12023-11-22T12:07:07ZengMDPI AGBiomedicines2227-90592021-08-0199109810.3390/biomedicines9091098<i>Lactococcus lactis</i> Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune RepertoireAnanta Prasad Arukha0Christian Furlan Freguia1Meerambika Mishra2Jyoti K. Jha3Subhashinie Kariyawasam4Neil A. Fanger5Ellen M. Zimmermann6Gary R. Fanger7Bikash Sahay8Department of Infectious Diseases and Immunology, University of Florida, Gainesville, FL 32608, USARise Therapeutics, Rockville, MD 20850, USADepartment of Infectious Diseases and Immunology, University of Florida, Gainesville, FL 32608, USARise Therapeutics, Rockville, MD 20850, USAComparative, Diagnostic and Population Medicine, University of Florida, Gainesville, FL 32608, USAVirtici, Seattle, WA 98122, USADivision of Gastroenterology, University of Florida College of Medicine, Gainesville, FL 32608, USARise Therapeutics, Rockville, MD 20850, USADepartment of Infectious Diseases and Immunology, University of Florida, Gainesville, FL 32608, USAInflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation comprised of Crohn’s disease and ulcerative colitis. Centers for Disease Control and Prevention report that 1.3% of the population of the United States (approximately 3 million people) were affected by the disease in 2015, and the number keeps increasing over time. IBD has a multifactorial etiology, from genetic to environmental factors. Most of the IBD treatments revolve around disease management, by reducing the inflammatory signals. We previously identified the surface layer protein A (SlpA) of <i>Lactobacillus acidophilus</i> that possesses anti-inflammatory properties to mitigate murine colitis. Herein, we expressed SlpA in a clinically relevant, food-grade <i>Lactococcus lactis</i> to further investigate and characterize the protective mechanisms of the actions of SlpA. Oral administration of SlpA-expressing <i>L. lactis</i> (R110) mitigated the symptoms of murine colitis. Oral delivery of R110 resulted in a higher expression of IL-27 by myeloid cells, with a synchronous increase in IL-10 and cMAF in T cells. Consistent with murine studies, human dendritic cells exposed to R110 showed exquisite differential gene regulation, including IL-27 transcription, suggesting a shared mechanism between the two species, hence positioning R110 as potentially effective at treating colitis in humans.https://www.mdpi.com/2227-9059/9/9/1098colitis<i>Lactococcus</i>microbiome |
| spellingShingle | Ananta Prasad Arukha Christian Furlan Freguia Meerambika Mishra Jyoti K. Jha Subhashinie Kariyawasam Neil A. Fanger Ellen M. Zimmermann Gary R. Fanger Bikash Sahay <i>Lactococcus lactis</i> Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune Repertoire Biomedicines colitis <i>Lactococcus</i> microbiome |
| title | <i>Lactococcus lactis</i> Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune Repertoire |
| title_full | <i>Lactococcus lactis</i> Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune Repertoire |
| title_fullStr | <i>Lactococcus lactis</i> Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune Repertoire |
| title_full_unstemmed | <i>Lactococcus lactis</i> Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune Repertoire |
| title_short | <i>Lactococcus lactis</i> Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune Repertoire |
| title_sort | i lactococcus lactis i delivery of surface layer protein a protects mice from colitis by re setting host immune repertoire |
| topic | colitis <i>Lactococcus</i> microbiome |
| url | https://www.mdpi.com/2227-9059/9/9/1098 |
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