Longitudinal Changes in Tear Cytokines and Antimicrobial Proteins in Trachomatous Disease

Abstract

Abstract Background Trachoma is a neglected tropical disease caused by ocular infection with Chlamydia trachomatis, where repeated infections and chronic inflammation can ultimately result in scarring, trichiasis and blindness. While scarring is thought to be mediated by a dysregulated immune response, the kinetics of cytokines and antimicrobial proteins in the tear film have not yet been characterised. Methods Pooled tears from a Gambian cohort and Tanzanian cohort were semi-quantitatively screened using a Proteome Profiler Array to identify cytokines differentially regulated in disease. Based on this screen and previous literature, ten cytokines (CXCL1, IP10, IFN-γ, IL1β, IL8, IL10, IL12p40, IL1RA, IL1α and PDGF), lysozyme and lactoferrin were assayed in the Tanzanian cohort by multiplex cytokine assay and ELISA. Finally, CXCL1, IP10, IL8, lysozyme and lactoferrin were longitudinally profiled in the Gambian cohort by multiplex cytokine assay and ELISA. Results In the Tanzanian cohort, IL8 was significantly raised in those with clinically inapparent infection (p = 0.0086). Lysozyme, IL10 and chemokines CXCL1, IL8, and IP10 were raised in scarring (p = 0.016, 0.046, 0.016, 0.037 and 0.093). CXCL1, IP10, IL8, lysozyme and lactoferrin were longitudinally profiled over the course of infection in a Gambian cohort study, with evidence of an inflammatory response both before, during and after detectable infection. CXCL1, IL8 and IP10 were raised in the second infection episode relative to the first (p = 0.0012, 0.044, and 0.04). Conclusions These findings suggest that the ocular immune system responds prior to and continues to respond after detectable C. trachomatis infection, possibly due to a positive feedback loop inducing immune activation. Levels of CXC chemokines in successive infection episodes were increased, which may offer an explanation as to why repeated infections are a risk factor for scarring.