July 10, 2017Immunology
For years, the ocular surface was thought to be sterile because of the presence of an enzyme called lysozyme that destroys bacteria, antimicrobial peptides, and other factors that rid the eye of microbes that may land from the air (or from our fingers) onto the surface of the eye.
According to an article published in the journal Immunity (27 June 2017), a study has demonstrated the existence of a resident ocular microbiome that trains the developing immune system to fend off pathogens. And yes there is a resident microbe living on the surface of the eye that protects the cornea from infection. According to the authors, this is the first evidence that a bacterium can live for a long time on the ocular surface, and that this study addresses a longstanding question about whether there is a resident ocular microbiome.
For the study, the authors were able to culture bacteria from the mouse conjunctiva, the membrane that lines the eyelids, and they found several species of Staphylococci, which are commonly found on the skin, and Corynebacterium mastitidis (C. mast). However, it wasn't clear whether those microbes had just arrived on the eye and were en route to being destroyed, or whether they lived on the eye for extended periods of time. During the study, the authors found that C. mast, when cultured with immune cells from the conjunctiva, induced the production of interleukin (IL)-17, a signaling protein critical for host defense. Upon further investigation, they found that IL-17 was produced by gamma delta T cells, a type of immune cell found in mucosal tissues. IL-17 attracted other immune cells called neutrophils -- the most abundant type of white blood cell -- to the conjunctiva and induced the release of anti-microbial proteins into the tears. The authors are currently investigating the unique features that can make C. mast resistant to the immune response that it itself provokes and allow it to persist in the eye.
To determine whether the microbe was contributing to the immune response in mice, the authors formed two groups, one control (with C. mast) and one treated with an antibiotic to kill C. mast and other ocular bacteria, and then challenged them with the fungus, Candida albicans. The mice receiving antibiotics had a reduced immune response in their conjunctiva and were not able to eliminate C. albicans, leading to full-blown ocular infection. The control mice with normal C. mast on the other hand were able to fend off the fungus. The authors also noticed that mice from the NIH animal facility had C. mast on their eyes, but mice from the Jackson Laboratory (JAX) in Maine and other commercial vendors did not. This fortuitous observation allowed the authors to determine if C. mast was truly a resident microbe, as opposed to a transient microbe that lands on the eye from the environment. They did this by inoculating C. mast-free mice with the microbe and determining if the microbe could be cultured from those animals' eyes many weeks later. They also determined whether the microbe could easily be transmitted among cagemates. When inoculated with C. mast, JAX mice produced conjunctival gamma delta T cells that released IL-17. Bacteria could still be cultured from their eyes after many weeks. By contrast, several other strains of bacteria inoculated onto the eyes of JAX mice disappeared without inducing local immunity. Interestingly, C. mast was not spread to cage-mates even after eight weeks of co-housing; however, C. mast can be passed from mother to pup. Both of these observations support the notion that C. mast is a resident commensal, not a bacterium that is continually re-introduced to the eye from the skin or the environment.
According to the authors, although C. mast appears to stimulate a beneficial immune response, there may be situations in which it could cause disease. For example, the elderly tend to have suppressed immune systems, which might allow C. mast to grow out of control and cause disease. The authors are currently investigating whether other bacteria play a role in regulating eye immunity.