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.

Department of Ophthalmology 1st Faculty of Medicine Charles University Prague and General University Hospital Prague U Nemocnice 2 12808 Prague 2 Czech Republic

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

Institute of Microbiology of the Czech Academy of Sciences v v i Prague Videnska 1083 14220 Prague 4 Czech Republic; Institute of Experimental Medicine of the Czech Academy of Sciences v v i Prague Videnska 1083 14220 Prague 4 Czech Republic

Section of Immunology and Infection Institute of Medical Sciences University of Aberdeen Foresterhill Aberdeen AB252ZD UK; Immunology and Virology Program Centre for Ophthalmology and Visual Science The University of Western Australia Crawley WA 6009 Australia; Centre for Experimental Immunology Lions Eye Institute 2 Verdun Street Nedlands WA 6009 Australia

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