Conjunctival Microbiome-Host Responses Are Associated With Impaired Epithelial Cell Health in Both Early and Late Stages of Trachoma - PubMed (original) (raw)

doi: 10.3389/fcimb.2019.00297. eCollection 2019.

Christine D Palmer 1, Joanna Houghton 1, Pateh Makalo 2, Hassan Joof 2, Tamsyn Derrick 1, Adriana Goncalves 1, David C W Mabey 1, Robin L Bailey 1, Matthew J Burton 1, Chrissy H Roberts 1, Sarah E Burr 1 2, Martin J Holland 1 2

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Conjunctival Microbiome-Host Responses Are Associated With Impaired Epithelial Cell Health in Both Early and Late Stages of Trachoma

Harry Pickering et al. Front Cell Infect Microbiol. 2019.

Abstract

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 hypothesized 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 type-2 interferon responses in scarring, whilst highlighting a common suppression of re-epithelialization with altered epithelial and bacterial adhesion, likely contributing to development of scarring pathology.

Keywords: conjunctival diseases; immune response; innate immunity; microbiome; trachoma.

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Figures

Figure 1

Figure 1

Fold-changes in conjunctival gene expression between cases and matched, healthy controls. Magnitude of fold-changes in conjunctival gene expression between children with active trachoma and healthy controls (A) and adults with scarring trachoma and healthy controls (B), shown by bars. Colors highlight increased (red) or decreased (blue) expression in cases. _P_-values were considered significant at <0.05 and are denominated as follows: *p < 0.05; **p < 0.01; and ***p < 0.001.

Figure 2

Figure 2

Comparison of fold-changes in conjunctival gene expression between active/scarring trachoma cases and healthy controls. Fold-changes in gene expression between children with active trachoma and healthy controls (orange bars) and adults with scarring trachoma and healthy controls (purple bars) are represented by bars with significance indicated as described below. Genes are sorted into three groups; downregulated in active and scarring trachoma (blue area), upregulated in active and scarring and trachoma (red area), and differentially regulated in active and scarring trachoma (green area). _P_-values were considered significant at <0.05 and are denominated as follows: *p < 0.05; **p < 0.01; and ***p < 0.001.

Figure 3

Figure 3

Relative abundance of major phyla in children and adults by case-control status. Phyla with relative abundance >1% in either children or adults are shown. Phyla with relative abundance ≤1% are grouped into “Other.”

Figure 4

Figure 4

Relative abundance of major genera in children and adults by case-control status. Genera with relative abundance >1% in either children or adults are shown. Genera with relative abundance ≤1% are grouped into “Other.”

Figure 5

Figure 5

Ocular microbiome diversity in children and adults by case-control status. Hill number at corresponding order of diversity are shown for cases (red) and healthy controls (blue) in children (A) and adults (B). Boxes represent the interquartile range, with median indicated (blue line). Outer bars represent the range. _P_-values were considered significant at <0.05 and are denominated as follows: *p < 0.05; **p < 0.01; and ***p < 0.001.

Figure 6

Figure 6

Plot of the ocular microbiome, modular conjunctival gene expression, and trachomatous disease in children. Non-metric multidimensional scaling of the complete ocular microbial community was used to position samples (points), enrichment of genera with relative abundance >1% are shown (black text). Arrows represent conjunctival gene expression modules (purple text), arrow coordinates indicate increased expression in surrounding samples. Shaded areas highlight the distribution of active trachoma (red) and healthy control (blue) samples.

Figure 7

Figure 7

Plot of the ocular microbiome, modular conjunctival gene expression, and trachomatous disease in adults. Non-metric multidimensional scaling of the complete ocular microbial community was used to position samples (points), enrichment of genera with relative abundance >1% are shown (black text). Arrows represent conjunctival gene expression modules (purple text), arrow coordinates indicate increased expression in surrounding samples. Shaded areas highlight the distribution of scarring trachoma (red) and healthy control (blue) samples.

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