Lysate of Parabacteroides distasonis prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of T cell response

The gut microbiota influences the reactivity of the immune system, and Parabacteroides distasonis has emerged as an anti-inflammatory commensal. Here, we investigated whether its lysate could prevent severe forms of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in mice and how...

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Main Authors: Zuzana Jiraskova Zakostelska, Michal Kraus, Stepan Coufal, Petra Prochazkova, Zaneta Slavickova, Tomas Thon, Tomas Hrncir, Jakub Kreisinger, Klara Kostovcikova, Pavlina Kleinova, Jana Lizrova Preiningerova, Miluse Pavelcova, Veronika Ticha, Ivana Kovarova, Eva Kubala Havrdova, Helena Tlaskalova-Hogenova, Miloslav Kverka
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1475126/full
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author Zuzana Jiraskova Zakostelska
Michal Kraus
Stepan Coufal
Petra Prochazkova
Zaneta Slavickova
Tomas Thon
Tomas Hrncir
Jakub Kreisinger
Klara Kostovcikova
Pavlina Kleinova
Jana Lizrova Preiningerova
Miluse Pavelcova
Veronika Ticha
Ivana Kovarova
Eva Kubala Havrdova
Helena Tlaskalova-Hogenova
Miloslav Kverka
author_facet Zuzana Jiraskova Zakostelska
Michal Kraus
Stepan Coufal
Petra Prochazkova
Zaneta Slavickova
Tomas Thon
Tomas Hrncir
Jakub Kreisinger
Klara Kostovcikova
Pavlina Kleinova
Jana Lizrova Preiningerova
Miluse Pavelcova
Veronika Ticha
Ivana Kovarova
Eva Kubala Havrdova
Helena Tlaskalova-Hogenova
Miloslav Kverka
author_sort Zuzana Jiraskova Zakostelska
collection DOAJ
description The gut microbiota influences the reactivity of the immune system, and Parabacteroides distasonis has emerged as an anti-inflammatory commensal. Here, we investigated whether its lysate could prevent severe forms of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in mice and how this preventive strategy affects the gut microbiota and immune response. Lysate of anaerobically cultured P. distasonis (Pd lysate) was orally administered to C57BL/6 mice in four weekly doses. One week later, EAE was induced and disease severity was assessed three weeks after induction. Fecal microbiota changes in both vehicle- and Pd lysate-treated animals was analyzed by 16S V3–V4 amplicon sequencing and qPCR, antimicrobial peptide expression in the intestinal mucosa was measured by qPCR, and immune cell composition in the mesenteric and inguinal lymph nodes was measured by multicolor flow cytometry. Pd lysate significantly delayed the development of EAE and reduced its severity when administered prior to disease induction. EAE induction was the main factor in altering the gut microbiota, decreasing the abundance of lactobacilli and segmented filamentous bacteria. Pd lysate significantly increased the intestinal abundance of the genera Anaerostipes, Parabacteroides and Prevotella, and altered the expression of antimicrobial peptides in the intestinal mucosa. It significantly increased the frequency of regulatory T cells, induced an anti-inflammatory milieu in mesenteric lymph nodes, and reduced the activation of T cells at the priming site. Pd lysate prevents severe forms of EAE by triggering a T regulatory response and modulating T cell priming to autoantigens. Pd lysate could thus be a future modulator of neuroinflammation that increases the resistance to multiple sclerosis.
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spelling doaj-art-97ff8d58fcf64dfeb21157fb3d3918492025-08-20T01:56:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14751261475126Lysate of Parabacteroides distasonis prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of T cell responseZuzana Jiraskova Zakostelska0Michal Kraus1Stepan Coufal2Petra Prochazkova3Zaneta Slavickova4Tomas Thon5Tomas Hrncir6Jakub Kreisinger7Klara Kostovcikova8Pavlina Kleinova9Jana Lizrova Preiningerova10Miluse Pavelcova11Veronika Ticha12Ivana Kovarova13Eva Kubala Havrdova14Helena Tlaskalova-Hogenova15Miloslav Kverka16Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, CzechiaLaboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, CzechiaLaboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, CzechiaLaboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, CzechiaLaboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, CzechiaLaboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, CzechiaLaboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, Novy Hradek, CzechiaLaboratory of Animal Evolutionary Biology, Department of Zoology, Faculty of Science, Charles University, Prague, CzechiaLaboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Medical Faculty, Charles University and General Medical Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Medical Faculty, Charles University and General Medical Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Medical Faculty, Charles University and General Medical Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Medical Faculty, Charles University and General Medical Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Medical Faculty, Charles University and General Medical Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Medical Faculty, Charles University and General Medical Hospital in Prague, Prague, CzechiaLaboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, CzechiaLaboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, CzechiaThe gut microbiota influences the reactivity of the immune system, and Parabacteroides distasonis has emerged as an anti-inflammatory commensal. Here, we investigated whether its lysate could prevent severe forms of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in mice and how this preventive strategy affects the gut microbiota and immune response. Lysate of anaerobically cultured P. distasonis (Pd lysate) was orally administered to C57BL/6 mice in four weekly doses. One week later, EAE was induced and disease severity was assessed three weeks after induction. Fecal microbiota changes in both vehicle- and Pd lysate-treated animals was analyzed by 16S V3–V4 amplicon sequencing and qPCR, antimicrobial peptide expression in the intestinal mucosa was measured by qPCR, and immune cell composition in the mesenteric and inguinal lymph nodes was measured by multicolor flow cytometry. Pd lysate significantly delayed the development of EAE and reduced its severity when administered prior to disease induction. EAE induction was the main factor in altering the gut microbiota, decreasing the abundance of lactobacilli and segmented filamentous bacteria. Pd lysate significantly increased the intestinal abundance of the genera Anaerostipes, Parabacteroides and Prevotella, and altered the expression of antimicrobial peptides in the intestinal mucosa. It significantly increased the frequency of regulatory T cells, induced an anti-inflammatory milieu in mesenteric lymph nodes, and reduced the activation of T cells at the priming site. Pd lysate prevents severe forms of EAE by triggering a T regulatory response and modulating T cell priming to autoantigens. Pd lysate could thus be a future modulator of neuroinflammation that increases the resistance to multiple sclerosis.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1475126/fullmultiple sclerosisexperimental autoimmune encephalomyelitisinflammationParabacteroides distasonismicrobiotaregulatory T cells
spellingShingle Zuzana Jiraskova Zakostelska
Michal Kraus
Stepan Coufal
Petra Prochazkova
Zaneta Slavickova
Tomas Thon
Tomas Hrncir
Jakub Kreisinger
Klara Kostovcikova
Pavlina Kleinova
Jana Lizrova Preiningerova
Miluse Pavelcova
Veronika Ticha
Ivana Kovarova
Eva Kubala Havrdova
Helena Tlaskalova-Hogenova
Miloslav Kverka
Lysate of Parabacteroides distasonis prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of T cell response
Frontiers in Immunology
multiple sclerosis
experimental autoimmune encephalomyelitis
inflammation
Parabacteroides distasonis
microbiota
regulatory T cells
title Lysate of Parabacteroides distasonis prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of T cell response
title_full Lysate of Parabacteroides distasonis prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of T cell response
title_fullStr Lysate of Parabacteroides distasonis prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of T cell response
title_full_unstemmed Lysate of Parabacteroides distasonis prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of T cell response
title_short Lysate of Parabacteroides distasonis prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of T cell response
title_sort lysate of parabacteroides distasonis prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of t cell response
topic multiple sclerosis
experimental autoimmune encephalomyelitis
inflammation
Parabacteroides distasonis
microbiota
regulatory T cells
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1475126/full
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