Genetically engineered eye-colonizing microbes that deliver the anti-inflammatory cytokine interleukin-10 enhance...

Barrier surfaces harbor tissue-colonizing microbes that can shape local physiology and immunity. During corneal injury, inflammation can delay healing, resulting in loss of visual acuity. Standards of care include topical applications of therapies, which are quickly washed away, requiring a laborious treatment regimen to maintain efficacy. To address this problem, we engineered an eye-colonizing microbe, Corynebacterium mastitidis, to act as a long-term therapeutic delivery vehicle by secreting bioactive interleukin (IL)-10 using a native secretion signal that we identified using transposon mutagenesis. Engineered microbes stably colonize the eye and release mouse (mIL-10) or human IL-10 (hIL-10) that modulates local immunity and accelerates wound repair after an initial inoculation event. Further, hIL-10 producing C. mast can regulate inflammatory cytokine production in immune cells, highlighting the immune-regulatory capabilities of this live biotherapeutic product. These findings demonstrate that genetically engineered eye-colonizing bacteria can serve as a self-sustaining therapeutic platform to control inflammation and promote tissue repair.