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Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria

The gastrointestinal tract represents one of the largest body surfaces that is exposed to the outside world. It is the only mucosal surface that is required to simultaneously recognize and defend against pathogens, while allowing nutrients containing foreign antigens to be tolerated and absorbed. It...

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Autores principales: Ramani, Kritika, Cormack, Taylor, Cartwright, Adam N. R., Alami, Aula, Parameswaran, Pooja, Abdou, Marynawal, Wang, Iris, Hilliard-Barth, Kristie, Argueta, Shannon, Raghunathan, Divya, Caffry, Will, Davitt, Christopher J. H., Romano, Fabian B., Ng, Aylwin, Kravitz, Valeria, Rommel, Tyler, Sizova, Maria, Kiran, Esra Uckun, Pradeep, Pallavi, Ponichtera, Holly E., Ganguly, Tanmoy, Bodmer, Mark, Itano, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847375/
https://www.ncbi.nlm.nih.gov/pubmed/35185874
http://dx.doi.org/10.3389/fimmu.2022.768076
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author Ramani, Kritika
Cormack, Taylor
Cartwright, Adam N. R.
Alami, Aula
Parameswaran, Pooja
Abdou, Marynawal
Wang, Iris
Hilliard-Barth, Kristie
Argueta, Shannon
Raghunathan, Divya
Caffry, Will
Davitt, Christopher J. H.
Romano, Fabian B.
Ng, Aylwin
Kravitz, Valeria
Rommel, Tyler
Sizova, Maria
Kiran, Esra Uckun
Pradeep, Pallavi
Ponichtera, Holly E.
Ganguly, Tanmoy
Bodmer, Mark
Itano, Andrea
author_facet Ramani, Kritika
Cormack, Taylor
Cartwright, Adam N. R.
Alami, Aula
Parameswaran, Pooja
Abdou, Marynawal
Wang, Iris
Hilliard-Barth, Kristie
Argueta, Shannon
Raghunathan, Divya
Caffry, Will
Davitt, Christopher J. H.
Romano, Fabian B.
Ng, Aylwin
Kravitz, Valeria
Rommel, Tyler
Sizova, Maria
Kiran, Esra Uckun
Pradeep, Pallavi
Ponichtera, Holly E.
Ganguly, Tanmoy
Bodmer, Mark
Itano, Andrea
author_sort Ramani, Kritika
collection PubMed
description The gastrointestinal tract represents one of the largest body surfaces that is exposed to the outside world. It is the only mucosal surface that is required to simultaneously recognize and defend against pathogens, while allowing nutrients containing foreign antigens to be tolerated and absorbed. It differentiates between these foreign substances through a complex system of pattern recognition receptors expressed on the surface of the intestinal epithelial cells as well as the underlying immune cells. These immune cells actively sample and evaluate microbes and other particles that pass through the lumen of the gut. This local sensing system is part of a broader distributed signaling system that is connected to the rest of the body through the enteric nervous system, the immune system, and the metabolic system. While local tissue homeostasis is maintained by commensal bacteria that colonize the gut, colonization itself may not be required for the activation of distributed signaling networks that can result in modulation of peripheral inflammation. Herein, we describe the ability of a gut-restricted strain of commensal bacteria to drive systemic anti-inflammatory effects in a manner that does not rely upon its ability to colonize the gastrointestinal tract or alter the mucosal microbiome. Orally administered EDP1867, a gamma-irradiated strain of Veillonella parvula, rapidly transits through the murine gut without colonization or alteration of the background microbiome flora. In murine models of inflammatory disease including delayed-type hypersensitivity (DTH), atopic dermatitis, psoriasis, and experimental autoimmune encephalomyelitis (EAE), treatment with EDP1867 resulted in significant reduction in inflammation and immunopathology. Ex vivo cytokine analyses revealed that EDP1867 treatment diminished production of pro-inflammatory cytokines involved in inflammatory cascades. Furthermore, blockade of lymphocyte migration to the gut-associated lymphoid tissues impaired the ability of EDP1867 to resolve peripheral inflammation, supporting the hypothesis that circulating immune cells are responsible for promulgating the signals from the gut to peripheral tissues. Finally, we show that adoptively transferred T cells from EDP1867-treated mice inhibit inflammation induced in recipient mice. These results demonstrate that an orally-delivered, non-viable strain of commensal bacteria can mediate potent anti-inflammatory effects in peripheral tissues through transient occupancy of the gastrointestinal tract, and support the development of non-living bacterial strains for therapeutic applications.
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spelling pubmed-88473752022-02-17 Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria Ramani, Kritika Cormack, Taylor Cartwright, Adam N. R. Alami, Aula Parameswaran, Pooja Abdou, Marynawal Wang, Iris Hilliard-Barth, Kristie Argueta, Shannon Raghunathan, Divya Caffry, Will Davitt, Christopher J. H. Romano, Fabian B. Ng, Aylwin Kravitz, Valeria Rommel, Tyler Sizova, Maria Kiran, Esra Uckun Pradeep, Pallavi Ponichtera, Holly E. Ganguly, Tanmoy Bodmer, Mark Itano, Andrea Front Immunol Immunology The gastrointestinal tract represents one of the largest body surfaces that is exposed to the outside world. It is the only mucosal surface that is required to simultaneously recognize and defend against pathogens, while allowing nutrients containing foreign antigens to be tolerated and absorbed. It differentiates between these foreign substances through a complex system of pattern recognition receptors expressed on the surface of the intestinal epithelial cells as well as the underlying immune cells. These immune cells actively sample and evaluate microbes and other particles that pass through the lumen of the gut. This local sensing system is part of a broader distributed signaling system that is connected to the rest of the body through the enteric nervous system, the immune system, and the metabolic system. While local tissue homeostasis is maintained by commensal bacteria that colonize the gut, colonization itself may not be required for the activation of distributed signaling networks that can result in modulation of peripheral inflammation. Herein, we describe the ability of a gut-restricted strain of commensal bacteria to drive systemic anti-inflammatory effects in a manner that does not rely upon its ability to colonize the gastrointestinal tract or alter the mucosal microbiome. Orally administered EDP1867, a gamma-irradiated strain of Veillonella parvula, rapidly transits through the murine gut without colonization or alteration of the background microbiome flora. In murine models of inflammatory disease including delayed-type hypersensitivity (DTH), atopic dermatitis, psoriasis, and experimental autoimmune encephalomyelitis (EAE), treatment with EDP1867 resulted in significant reduction in inflammation and immunopathology. Ex vivo cytokine analyses revealed that EDP1867 treatment diminished production of pro-inflammatory cytokines involved in inflammatory cascades. Furthermore, blockade of lymphocyte migration to the gut-associated lymphoid tissues impaired the ability of EDP1867 to resolve peripheral inflammation, supporting the hypothesis that circulating immune cells are responsible for promulgating the signals from the gut to peripheral tissues. Finally, we show that adoptively transferred T cells from EDP1867-treated mice inhibit inflammation induced in recipient mice. These results demonstrate that an orally-delivered, non-viable strain of commensal bacteria can mediate potent anti-inflammatory effects in peripheral tissues through transient occupancy of the gastrointestinal tract, and support the development of non-living bacterial strains for therapeutic applications. Frontiers Media S.A. 2022-02-02 /pmc/articles/PMC8847375/ /pubmed/35185874 http://dx.doi.org/10.3389/fimmu.2022.768076 Text en Copyright © 2022 Ramani, Cormack, Cartwright, Alami, Parameswaran, Abdou, Wang, Hilliard-Barth, Argueta, Raghunathan, Caffry, Davitt, Romano, Ng, Kravitz, Rommel, Sizova, Kiran, Pradeep, Ponichtera, Ganguly, Bodmer and Itano https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ramani, Kritika
Cormack, Taylor
Cartwright, Adam N. R.
Alami, Aula
Parameswaran, Pooja
Abdou, Marynawal
Wang, Iris
Hilliard-Barth, Kristie
Argueta, Shannon
Raghunathan, Divya
Caffry, Will
Davitt, Christopher J. H.
Romano, Fabian B.
Ng, Aylwin
Kravitz, Valeria
Rommel, Tyler
Sizova, Maria
Kiran, Esra Uckun
Pradeep, Pallavi
Ponichtera, Holly E.
Ganguly, Tanmoy
Bodmer, Mark
Itano, Andrea
Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria
title Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria
title_full Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria
title_fullStr Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria
title_full_unstemmed Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria
title_short Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria
title_sort regulation of peripheral inflammation by a non-viable, non-colonizing strain of commensal bacteria
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847375/
https://www.ncbi.nlm.nih.gov/pubmed/35185874
http://dx.doi.org/10.3389/fimmu.2022.768076
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