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Journal of Immunology Research
Volume 2016 (2016), Article ID 5065703, 11 pages
http://dx.doi.org/10.1155/2016/5065703
Research Article

The Microbiota Determines Susceptibility to Experimental Autoimmune Uveoretinitis

1Department of Ophthalmology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 12808 Prague 2, Czech Republic
2Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague, Videnska 1083, 14220 Prague 4, Czech Republic
3Institute of Experimental Medicine of the Czech Academy of Sciences, v.v.i., Prague, Videnska 1083, 14220 Prague 4, Czech Republic
4Section of Immunology and Infection, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB252ZD, UK
5Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA 6009, Australia
6Centre for Experimental Immunology, Lions Eye Institute, 2 Verdun Street, Nedlands, WA 6009, Australia

Received 30 November 2015; Revised 8 March 2016; Accepted 11 April 2016

Academic Editor: Xiao-Feng Yang

Copyright © 2016 Jarmila Heissigerova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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-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.