Active Trachoma Is Associated with Increased Conjunctival Expression of<i>IL17A</i>and Profibrotic Cytokines

Burton, Matthew J.; Ramadhani, Athumani; Weiss, Helen A.; Hu, Victor; Massae, Patrick; Burr, Sarah E.; Shangali, Wahida; Holland, Martin J.; Mabey, David; Bailey, Robin L.

doi:10.1128/iai.05718-11

Cited by 46 publications

(56 citation statements)

References 62 publications

(101 reference statements)

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“…In turn, IL-17 inhibits miR-23b, leading to inflammation. An up-regulation of IL-17A is associated with active trachomatous disease [30]. The relative down-regulation of miR-23b in TSI compared to TS and N conjunctival samples could reflect a down-regulation of this miR's expression by IL-17 in individuals with TSI.…”

Section: Discussionmentioning

confidence: 99%

Conjunctival MicroRNA Expression in Inflammatory Trachomatous Scarring

et al. 2013

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PurposeTrachoma is a fibrotic disease of the conjunctiva initiated by Chlamydia trachomatis infection. This blinding disease affects over 40 million people worldwide yet the mechanisms underlying its pathogenesis remain poorly understood. We have investigated host microRNA (miR) expression in health (N) and disease (conjunctival scarring with (TSI) and without (TS) inflammation) to determine if these epigenetic differences are associated with pathology.MethodsWe collected two independent samples of human conjunctival swab specimens from individuals living in The Gambia (n = 63 & 194). miR was extracted, and we investigated the expression of 754 miR in the first sample of 63 specimens (23 N, 17 TS, 23 TSI) using Taqman qPCR array human miRNA genecards. Network and pathway analysis was performed on this dataset. Seven miR that were significantly differentially expressed between different phenotypic groups were then selected for validation by qPCR in the second sample of 194 specimens (93 N, 74 TS, 22 TSI).ResultsArray screening revealed differential expression of 82 miR between N, TS and TSI phenotypes (fold change >3, p<0.05). Predicted mRNA targets of these miR were enriched in pathways involved in fibrosis and epithelial cell differentiation. Two miR were confirmed as being differentially expressed upon validation by qPCR. miR-147b is significantly up-regulated in TSI versus N (fold change = 2.3, p = 0.03) and miR-1285 is up-regulated in TSI versus TS (fold change = 4.6, p = 0.005), which was consistent with the results of the qPCR array.ConclusionsmiR-147b and miR-1285 are up-regulated in inflammatory trachomatous scarring. Further investigation of the function of these miR will aid our understanding of the pathogenesis of trachoma.

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Section: Discussionmentioning

confidence: 99%

Conjunctival MicroRNA Expression in Inflammatory Trachomatous Scarring

et al. 2013

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“…In a clinical study investigating active trachoma, gene expression of ENA-78 was increased [54]. The authors postulated that ENA-78 might contribute to fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Water-Filtered Infrared A Irradiation in Combination with Visible Light Inhibits Acute Chlamydial Infection

et al. 2014

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New therapeutic strategies are needed to overcome drawbacks in treatment of infections with intracellular bacteria. Chlamydiaceae are Gram-negative bacteria implicated in acute and chronic diseases such as abortion in animals and trachoma in humans. Water-filtered infrared A (wIRA) is short wavelength infrared radiation with a spectrum ranging from 780 to 1400 nm. In clinical settings, wIRA alone and in combination with visible light (VIS) has proven its efficacy in acute and chronic wound healing processes. This is the first study to demonstrate that wIRA irradiation combined with VIS (wIRA/VIS) diminishes recovery of infectious elementary bodies (EBs) of both intra- and extracellular Chlamydia (C.) in two different cell lines (Vero, HeLa) regardless of the chlamydial strain (C. pecorum, C. trachomatis serovar E) as shown by indirect immunofluorescence and titration by subpassage. Moreover, a single exposure to wIRA/VIS at 40 hours post infection (hpi) led to a significant reduction of C. pecorum inclusion frequency in Vero cells and C. trachomatis in HeLa cells, respectively. A triple dose of irradiation (24, 36, 40 hpi) during the course of C. trachomatis infection further reduced chlamydial inclusion frequency in HeLa cells without inducing the chlamydial persistence/stress response, as ascertained by electron microscopy. Irradiation of host cells (HeLa, Vero) neither affected cell viability nor induced any molecular markers of cytotoxicity as investigated by Alamar blue assay and Western blot analysis. Chlamydial infection, irradiation, and the combination of both showed a similar release pattern of a subset of pro-inflammatory cytokines (MIF/GIF, Serpin E1, RANTES, IL-6, IL-8) and chemokines (IL-16, IP-10, ENA-78, MIG, MIP-1α/β) from host cells. Initial investigation into the mechanism indicated possible thermal effects on Chlamydia due to irradiation. In summary, we demonstrate a non-chemical reduction of chlamydial infection using the combination of water-filtered infrared A and visible light.

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“…In a study in The Gambia, active trachoma was associated with increased expression of profibrotic cytokines and IL17A, which is proinflammatory in both innate and adaptive immune responses. [20]. …”

Section: Etiology and Immunopathology Of Clinical Signsmentioning

confidence: 99%

Trachoma

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Gaynor

et al. 2012

Current Opinion in Ophthalmology

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Purpose of review To review recent clinical and epidemiological studies regarding the prevention, diagnosis, and treatment of trachoma. Recent Findings Newer studies propose novel diagnostic tests that appear sensitive for the detection of ocular chlamydial infection. Immunologic studies suggest that chronic inflammation can lead to progressive scarring, even in the absence of chlamydia. Confocal microscopy can obtain accurate grading of scarring progression. Mass oral azithromycin distributions remain a mainstay of treatment; studies have assessed the appropriate frequency and duration of treatment programs. Current studies have also explored ancillary effects of azithromycin distribution on mortality and bacterial infections. Summary Trachoma programs have had remarkable success at reducing chlamydial infection and clinical signs of trachoma. Recent work suggests improved methods to monitor infection and scarring, and better ways to distribute treatment. While studies continue to demonstrate reduction in infection in hyperendemic areas, more work will need to be done to achieve elimination of this blinding disease.

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Active Trachoma Is Associated with Increased Conjunctival Expression ofIL17Aand Profibrotic Cytokines

Cited by 46 publications

References 62 publications

Conjunctival MicroRNA Expression in Inflammatory Trachomatous Scarring

Conjunctival MicroRNA Expression in Inflammatory Trachomatous Scarring

Water-Filtered Infrared A Irradiation in Combination with Visible Light Inhibits Acute Chlamydial Infection

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