Role of Microbiota in Strengthening Ocular Mucosal Barrier Function Through Secretory IgA
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CitationWright, Quentin George. 2017. Role of Microbiota in Strengthening Ocular Mucosal Barrier Function Through Secretory IgA. Master's thesis, Harvard Extension School.
AbstractUnlike other mucosal sites, the ocular mucosal surfaces are paucibacterial, which suggests that effective cellular and molecular mechanisms ensure limited commensal presence. Given that secretory IgA (SIgA) is a major component of the ocular tear film, it was of interest to identify factors and mechanisms that govern ocular SIgA generation and abundance. Quantitative proteomic analysis of ocular surface washes from mice of different genetic backgrounds (C57BL/6N, Swiss Webster (SW) and BALB/c) revealed that tear film SIgA concentrations were dependent on genetic background but considerably influenced by microbiota. Ocular surface SIgA concentrations were significantly more prevalent in SW mice when compared to C57BL/6N mice. Consistently, Swiss Webster’s, BALB/c’s and C57BL/6N’s were having the highest to lowest IgA gene expression in the lacrimal glands respectively. Analysis of the impact of microbiota on SIgA in the tear film within a specific genetic environment (e.g., SPF SW mice) showed that commensals promoted ocular surface SIgA levels. Oral antibiotic cocktail intake that reduced significantly gut commensal presence, while maintaining ocular surface commensal levels, reduced ocular surface SIgA protein and IgA transcript levels in the LGs in specific pathogen free (SPF) SW mice illustrating a gut-eye axes of immune regulation.
To determine whether the presence of specific gut commensal species could influence IgA transcript levels in the LGs, we characterized the gut commensal communities of SPF SW mice. 16S sequencing revealed that SPF SW mice carried abundant and diverse Bacteriodies species when compared to C57BL6/N mice.
Among the most prominent species was Bacteriodies acidifaciens. Monocolonization of GF SW mice with B. acidifaciens, a strict gut anaerobe, resulted in an expected significant increase of IgA transcripts in the colon and, interestingly, measurable and significant increase of IgA transcripts in the LGs, implying generation of B cell memory. Analysis of the ocular surface washes from the reconstituted SW mice showed no significant increase in tear film SIgA levels, demonstrating the need for surface priming. Taken together, these data suggest that the ocular surfaces are paucibacterial, because exposure of the host to gut commensal species serves as a priming signal to generate B cell repertoire at sites different from the gut such as LGs, thereby ensuring broad protection. Local exposure to commensals may be needed to expand these memory responses.
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