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Mihaela G Gadjeva, Abirami Kugadas, Laura Ruiz, Sharmila Masli; Impact of microbiome on ocular immunity. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4845.
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© ARVO (1962-2015); The Authors (2016-present)
How microbiome affects the ocular immunity is at its early stage of accumulating experimental evidence. Here, we carried out experiments to evaluate the repertoire of ocular commensals in healthy mice, and autoimmune-prone mice. To determine the significance of microbiome in promoting health, we compared the susceptibility to infection of germ-free (GF) mice, conventional mice, and GF mice reconstituted with murine or human microbiota.
To characterize the ocular commensals in healthy mice and mice that develop Sjögren syndrome-like disease, conjunctival swabs were collected from the conventionally bred wild type (C57BL6) mice and thrombospondin-1 (Tsp-1 -/-) deficient mice and plated on selective agar media. To evaluate the ocular immune status of the different groups of mice, quantitative LC-MS/MS analysis of ocular surface proteomes were carried out. To evaluate the impact of microbiome on sensitivity to infection, mice were challenged with P. aeruginosa 6294, bacterial presence in the cornea and the degree of developed ocular pathology during keratitis were quantified.
We found that the repertoire of the ocular microbiota in mice was limited to Staphylococcus aureus, Staphylococcus coagulase negative sp, and Streptococcus sp. The Tsp-1-/- mice showed significant increase in Staphylococcus aureus, Staphylococcus coagulase negative sp ocular commensals, suggestive of a defect in the clearance mechanisms. Quantitative LC-MS/MS analysis of ocular surface proteomes demonstrated that in the absence of commensals, the tear-film components were altered. For example, complement pathway components and iron-scavenging proteins were significantly reduced in the GF animals. In agreement with this finding, the GF mice were more sensitive to ocular P. aeruginosa-induced keratitis than the conventional mice. This was exemplified by increased bacterial presence and elevated corneal pathology. Upon reconstitution of GF mice with either mouse or human microbiota, the resistance to infection and the levels of ocular innate immune mediators were recovered.
Our data suggest that tonic signals from local commensal flora continuously induce increased synthesis of ocular innate immune effectors to limit microbial presence at the ocular surfaces. Furthermore, when the host fails to limit commensal outgrowth, autoimmune disease states could occur.
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