Impact Factor 3.518 | CiteScore 3.62
More on impact ›

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00297

Conjunctival microbiome-host responses are associated with impaired epithelial cell health in both early and late stages of trachoma

 Harry Pickering1*, Christine D. Palmer1, Joanna Houghton1, Pateh Makalo2, Hassan Joof2,  Tamsyn Derrick1, Adriana Goncalves1, David C. Mabey1, Robin L. Bailey1,  Matthew J. Burton1, 3,  Chrissy h. Roberts1, Sarah E. Burr1, 2 and  Martin J. Holland1, 2
  • 1London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom
  • 2Disease Control and Elimination Theme, Medical Research Council The Gambia Unit (MRC), Gambia
  • 3Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom

Background
Trachoma, a neglected tropical disease, is the leading infectious cause of blindness and visual impairment worldwide. Host responses to ocular chlamydial infection resulting in chronic inflammation and expansion of non-chlamydial bacteria are hypothesised risk factors for development of active trachoma and conjunctival scarring

Methods
Ocular swabs from trachoma endemic populations in The Gambia were selected from archived samples for 16S sequencing and host conjunctival gene expression. We recruited children with active trachoma and adults with conjunctival scarring, alongside corresponding matched controls.

Findings
In children, active trachoma was not associated with significant changes in the ocular microbiome. Haemophilus enrichment was associated with antimicrobial responses but not linked to active trachoma. Adults with scarring trachoma had a reduced ocular bacterial diversity compared to controls, with increased relative abundance of Corynebacterium. Increased abundance of Corynebacterium in scarring disease was associated with innate immune responses to the microbiota, dominated by altered mucin expression and increased matrix adhesion.

Interpretation
In the absence of current Chlamydia trachomatis infection, changes in the ocular microbiome associate with differential expression of antimicrobial and inflammatory genes that impair epithelial cell health. In scarring trachoma, expansion of ‘non-pathogenic’ bacteria such as Corynebacterium and innate responses are coincident, warranting further investigation of this relationship. Comparisons between active and scarring trachoma supported the relative absence of interferon-gamma responses in scarring, whilst highlighting a common suppression of re-epithelialisation with altered epithelial and bacterial adhesion, likely contributing to development of scarring pathology.

Keywords: Trachoma, immune response, microbiome, innate immunity, conjunctival disease

Received: 02 Apr 2019; Accepted: 31 Jul 2019.

Edited by:

Matam Vijay-Kumar, University of Toledo, United States

Reviewed by:

Daniel C. Propheter, UT Southwestern Medical Center, United States
Fernando L. Leite, Boehringer Ingelheim Animal Health Business Unit, United States  

Copyright: © 2019 Pickering, Palmer, Houghton, Makalo, Joof, Derrick, Goncalves, Mabey, Bailey, Burton, Roberts, Burr and Holland. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Harry Pickering, London School of Hygiene and Tropical Medicine (LSHTM), London, United Kingdom, harry.pickering@lshtm.ac.uk