The Microbiota Determines Susceptibility to Experimental Autoimmune Uveoretinitis

Author:

Heissigerova Jarmila1,Seidler Stangova Petra1,Klimova Aneta1,Svozilkova Petra1,Hrncir Tomas2,Stepankova Renata2,Kverka Miloslav23,Tlaskalova-Hogenova Helena2,Forrester John V.456

Affiliation:

1. Department of Ophthalmology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 12808 Prague 2, Czech Republic

2. Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague, Videnska 1083, 14220 Prague 4, Czech Republic

3. Institute of Experimental Medicine of the Czech Academy of Sciences, v.v.i., Prague, Videnska 1083, 14220 Prague 4, Czech Republic

4. Section of Immunology and Infection, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB252ZD, UK

5. Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA 6009, Australia

6. Centre for Experimental Immunology, Lions Eye Institute, 2 Verdun Street, Nedlands, WA 6009, Australia

Abstract

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-γand 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.

Funder

Czech Science Foundation

Publisher

Hindawi Limited

Subject

Immunology,General Medicine,Immunology and Allergy

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