Abstract
Commensal bacteria play an important role in the formation of the immune system but their role in the maintenance of immune homeostasis at the ocular surface and lacrimal gland remains poorly understood. This study investigated the eye and lacrimal gland phenotype in germ-free and conventional C57BL/6J mice. Our results showed that germ-free mice had significantly greater corneal barrier disruption, greater goblet cell loss, and greater total inflammatory cell and CD4+ T cell infiltration within the lacrimal gland compared to the conventionally housed group. A greater frequency of CD4+IFN-γ+ cells was observed in germ-free lacrimal glands. Females exhibited a more severe phenotype compared to males. Adoptive transfer of CD4+ T cells isolated from female germ-free mice into RAG1KO mice transferred Sjögren-like lacrimal keratoconjunctivitis. Fecal microbiota transplant from conventional mice reverted dry eye phenotype in germ-free mice and decreased CD4+IFN-γ+ cells to levels similar to conventional C57BL/6J mice. These findings indicate that germ-free mice have a spontaneous lacrimal keratoconjunctivitis similar to that observed in Sjögren syndrome patients and demonstrate that commensal bacteria function in maintaining immune homeostasis on the ocular surface. Thus, manipulation of intestinal commensal bacteria has the potential to become a novel therapeutic approach to treat Sjögren Syndrome.
Highlights
There is increasing evidence indicating that the microbiome—the bacterial communities that inhabit the human body—plays key roles in the development and function of the immune system
We demonstrate that germ-free C57BL/6J mice have a spontaneous Sjögren-like lacrimal keratoconjunctivitis, with autoreactive T cells that can transmit the disease phenotype
We investigated the uptake of a fluorescent dye as a measurement of corneal permeability and examined Periodic acid–Schiff (PAS)-stained histologic sections from the conjunctival to measure conjunctival goblet cell density
Summary
There is increasing evidence indicating that the microbiome—the bacterial communities that inhabit the human body—plays key roles in the development and function of the immune system. Routine cultures from conjunctival swabs were negative in more than 50% of cases [1,2,3]. This was thought to be due to the high concentration of antimicrobial peptides and proteins in the tear film [4,5,6,7,8,9]. Most of the recent literature has pointed to a very small bacterial load on the ocular surface and a non-existent “core” ocular microbiome [1,10,11,12,13,14,15]. Recent studies have highlighted the importance of some eye commensal bacteria in the context of corneal infections in C57BL/6 mice [16,17,18,19]
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