Abstract
Purpose :
Tobramycin is frequently prescribed for ocular surface infections; however, the effect on commensal bacteria and host immunity is not well-understood. Using the known eye-colonizing microbe, Corynebacterium mastiditis (C. mast), we can assess how topical antibiotics may affect the ocular surface microenvironment. Here, we aim to determine the effect of tobramycin on C. mast colonization in vivo and to evaluate tobramycin’s immune modulating properties.
Methods :
6-week female mice were colonized with C. mast and later treated with an ophthalmic tobramycin solution to evaluate colonization persistence. We analyzed γδ+ T cells and neutrophils in control, colonized, recovery, and no recovery groups. For in vivo challenge, we infected groups of mice with Pseudomonas aeruginosa (Pa) and examined recruited myeloid cells, inflammatory markers, and bacteria CFU. For in vitro experiments, we evaluated direct effects of tobramycin on immune functionality of bone marrow-derived dendritic cells non-specifically stimulated γδ+ T cells.
Results :
In vivo, we found that C. mast load is undetectable in mice treated with tobramycin; however, C. mast returns to pre-treatment levels by 4 weeks after tobramycin treatment. Mice depleted of bacteria have significantly fewer neutrophils (p<0.01) and C. mast specific γδ+ T cells (p<0.01) compared to control colonized mice; however, these populations were re-established by 4 weeks after tobramycin treatment. Unexpectedly, 6-week recovery mice displayed similar protection against Pa challenge in terms of CFU burden as colonized mice; however, a more robust inflammatory response was mounted in 6-week recovery groups compared to controls. In vitro, we found that tobramycin can modulate immune functionality in a dose-dependent manner by inhibition the effector functions of DCs and gd+ T cells.
Conclusions :
Our results indicate that antibiotics decrease commensal bacteria load without complete elimination from the host. This creates a window of recovery for the commensal, but it also may create a window of susceptibility for the host from inhibited commensal immunity. In addition, there may be concerns over antibiotic use as the ocular immune system seems to be more inflammatory up to 6 weeks after antibiotic cessation. Our findings clarify unforeseen effects of antibiotics on commensal/immune interactions.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.