Ocular surface microflora modulates IL-17 and neutrophil recruitment within the conjunctiva associated lymphoid tissue

FARE Award Winner

Authors

• AJ St Leger
• RA Drummond
• JV Desai
• PB Silver
• RR Caspi

Abstract

Studies have suggested a critical role for the functionality of conjunctiva associated lymphoid tissue (CALT), a mucosal immune tissue of the ocular surface, to maintain ocular surface health. In this study, we developed a working mouse model to study the functional properties of CALT. Within the CALT at steady state, we showed that the tissue harbors IL-17 producing cells as well as monocytes such as neutrophils. Furthermore, we significantly inhibited steady state neutrophil recruitment to the CALT by giving a single subconjunctival (local) injection of neutralizing antibodies against IL-17. This result led to two conclusions: (1) that neutrophil recruitment to CALT requires IL-17A or F and (2) that, potentially, a microbial stimulant within the CALT continually induces IL-17 in the tissue. When we incubated a co-culture of FACS isolated CD11b+ dendritic cells and T cells from the CALT with various lysates from bacteria expanded from CALT, we found dose dependent increases in IL-17, which led to the assumption that microbes can, indeed, induce IL-17 in ocular mucosa. In vivo, we disrupted the normal ocular flora by local application of antibiotics for 5 days and found significant reductions in CALT-neutrophils and IL-17. This result was recapitulated in germfree (GF) mice. Finally, mice with a disrupted ocular microbiome are dramatically more susceptible to pathology associated with an ocular Candida Albicans infection. Our data, for the first time, provide a mechanistic description of the cross-talk between the CALT immune system and ocular commensal microflora as well as its critical implications to ocular disease.

Scientific Focus Area: Immunology

This page was last updated on Friday, March 26, 2021