The Microbiota Determines Susceptibility to Experimental Autoimmune Uveoretinitis

The microbiota is a crucial modulator of the immune system. Here, we evaluated how its absence or reduction modifies the inflammatory response in the murine model of experimental autoimmune uveoretinitis (EAU). We induced EAU in germ-free (GF) or conventionally housed (CV) mice and in CV mice treate...

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Main Authors: Jarmila Heissigerova, Petra Seidler Stangova, Aneta Klimova, Petra Svozilkova, Tomas Hrncir, Renata Stepankova, Miloslav Kverka, Helena Tlaskalova-Hogenova, John V. Forrester
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2016/5065703
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author Jarmila Heissigerova
Petra Seidler Stangova
Aneta Klimova
Petra Svozilkova
Tomas Hrncir
Renata Stepankova
Miloslav Kverka
Helena Tlaskalova-Hogenova
John V. Forrester
author_facet Jarmila Heissigerova
Petra Seidler Stangova
Aneta Klimova
Petra Svozilkova
Tomas Hrncir
Renata Stepankova
Miloslav Kverka
Helena Tlaskalova-Hogenova
John V. Forrester
author_sort Jarmila Heissigerova
collection DOAJ
description The microbiota is a crucial modulator of the immune system. Here, we evaluated how its absence or reduction modifies the inflammatory response in the murine model of experimental autoimmune uveoretinitis (EAU). We induced EAU in germ-free (GF) or conventionally housed (CV) mice and in CV mice treated with a combination of broad-spectrum antibiotics either from the day of EAU induction or from one week prior to induction of disease. The severity of the inflammation was assessed by fundus biomicroscopy or by histology, including immunohistology. The immunophenotyping of T cells in local and distant lymph nodes was performed by flow cytometry. We found that GF mice and mice where the microbiota was reduced one week before EAU induction were protected from severe autoimmune inflammation. GF mice had lower numbers of infiltrating macrophages and significantly less T cell infiltration in the retina than CV mice with EAU. GF mice also had reduced numbers of IFN-γ and IL-17-producing T cells and increased numbers of regulatory T cells in the eye-draining lymph nodes. These data suggest that the presence of microbiota during autoantigen recognition regulates the inflammatory response by influencing the adaptive immune response.
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spelling doaj-art-734e4313087e4b6c9304c8b257acd57a2025-02-03T01:10:14ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/50657035065703The Microbiota Determines Susceptibility to Experimental Autoimmune UveoretinitisJarmila Heissigerova0Petra Seidler Stangova1Aneta Klimova2Petra Svozilkova3Tomas Hrncir4Renata Stepankova5Miloslav Kverka6Helena Tlaskalova-Hogenova7John V. Forrester8Department of Ophthalmology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 12808 Prague 2, Czech RepublicDepartment of Ophthalmology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 12808 Prague 2, Czech RepublicDepartment of Ophthalmology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 12808 Prague 2, Czech RepublicDepartment of Ophthalmology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 12808 Prague 2, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague, Videnska 1083, 14220 Prague 4, Czech RepublicSection of Immunology and Infection, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB252ZD, UKThe microbiota is a crucial modulator of the immune system. Here, we evaluated how its absence or reduction modifies the inflammatory response in the murine model of experimental autoimmune uveoretinitis (EAU). We induced EAU in germ-free (GF) or conventionally housed (CV) mice and in CV mice treated with a combination of broad-spectrum antibiotics either from the day of EAU induction or from one week prior to induction of disease. The severity of the inflammation was assessed by fundus biomicroscopy or by histology, including immunohistology. The immunophenotyping of T cells in local and distant lymph nodes was performed by flow cytometry. We found that GF mice and mice where the microbiota was reduced one week before EAU induction were protected from severe autoimmune inflammation. GF mice had lower numbers of infiltrating macrophages and significantly less T cell infiltration in the retina than CV mice with EAU. GF mice also had reduced numbers of IFN-γ and IL-17-producing T cells and increased numbers of regulatory T cells in the eye-draining lymph nodes. These data suggest that the presence of microbiota during autoantigen recognition regulates the inflammatory response by influencing the adaptive immune response.http://dx.doi.org/10.1155/2016/5065703
spellingShingle Jarmila Heissigerova
Petra Seidler Stangova
Aneta Klimova
Petra Svozilkova
Tomas Hrncir
Renata Stepankova
Miloslav Kverka
Helena Tlaskalova-Hogenova
John V. Forrester
The Microbiota Determines Susceptibility to Experimental Autoimmune Uveoretinitis
Journal of Immunology Research
title The Microbiota Determines Susceptibility to Experimental Autoimmune Uveoretinitis
title_full The Microbiota Determines Susceptibility to Experimental Autoimmune Uveoretinitis
title_fullStr The Microbiota Determines Susceptibility to Experimental Autoimmune Uveoretinitis
title_full_unstemmed The Microbiota Determines Susceptibility to Experimental Autoimmune Uveoretinitis
title_short The Microbiota Determines Susceptibility to Experimental Autoimmune Uveoretinitis
title_sort microbiota determines susceptibility to experimental autoimmune uveoretinitis
url http://dx.doi.org/10.1155/2016/5065703
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