Longitudinal changes in tear cytokines and antimicrobial proteins in trachomatous disease.
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
20
02
2023
accepted:
28
09
2023
revised:
01
11
2023
medline:
3
11
2023
pubmed:
20
10
2023
entrez:
20
10
2023
Statut:
epublish
Résumé
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. 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, IP-10, IFN-γ, IL-1β, IL-8, IL-10, IL-12 p40, IL-1RA, IL-1α and PDGF), lysozyme and lactoferrin were assayed in the Tanzanian cohort by multiplex cytokine assay and ELISA. Finally, CXCL1, IP-10, IL-8, lysozyme and lactoferrin were longitudinally profiled in the Gambian cohort by multiplex cytokine assay and ELISA. In the Tanzanian cohort, IL-8 was significantly increased in those with clinically inapparent infection (p = 0.0086). Lysozyme, IL-10 and chemokines CXCL1 and IL-8 were increased in scarring (p = 0.016, 0.046, 0.016, and 0.037). CXCL1, IP-10, IL-8, 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, IL-8 and IP-10 were higher in the second infection episode relative to the first (p = 0.0012, 0.044, and 0.04). 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.
Sections du résumé
BACKGROUND
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.
METHODOLOGY
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, IP-10, IFN-γ, IL-1β, IL-8, IL-10, IL-12 p40, IL-1RA, IL-1α and PDGF), lysozyme and lactoferrin were assayed in the Tanzanian cohort by multiplex cytokine assay and ELISA. Finally, CXCL1, IP-10, IL-8, lysozyme and lactoferrin were longitudinally profiled in the Gambian cohort by multiplex cytokine assay and ELISA.
RESULTS
RESULTS
In the Tanzanian cohort, IL-8 was significantly increased in those with clinically inapparent infection (p = 0.0086). Lysozyme, IL-10 and chemokines CXCL1 and IL-8 were increased in scarring (p = 0.016, 0.046, 0.016, and 0.037). CXCL1, IP-10, IL-8, 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, IL-8 and IP-10 were higher in the second infection episode relative to the first (p = 0.0012, 0.044, and 0.04).
CONCLUSIONS
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.
Identifiants
pubmed: 37862368
doi: 10.1371/journal.pntd.0011689
pii: PNTD-D-23-00223
pmc: PMC10619880
doi:
Substances chimiques
Cytokines
0
Interleukin-10
130068-27-8
Muramidase
EC 3.2.1.17
Interleukin-8
0
Chemokine CXCL10
0
Lactoferrin
EC 3.4.21.-
Anti-Infective Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0011689Informations de copyright
Copyright: © 2023 Barton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Am J Reprod Immunol. 2011 Dec;66(6):534-43
pubmed: 21883620
JAMA Ophthalmol. 2017 Nov 1;135(11):1156-1162
pubmed: 28975236
Mol Vis. 2012;18:2717-25
pubmed: 23233782
Annu Rev Immunol. 2014;32:659-702
pubmed: 24655300
Sci Rep. 2020 Oct 26;10(1):18269
pubmed: 33106516
Nat Commun. 2021 Sep 15;12(1):5454
pubmed: 34526512
PLoS Negl Trop Dis. 2013;7(2):e2020
pubmed: 23457650
Eye (Lond). 1998;12 ( Pt 3a):453-60
pubmed: 9775249
Trop Med Int Health. 2010 Jun;15(6):673-91
pubmed: 20374566
Genes Immun. 2006 Apr;7(3):243-9
pubmed: 16525502
J Infect Dis. 2015 Jun 15;211(12):2014-22
pubmed: 25552370
Infect Immun. 2004 Dec;72(12):7352-6
pubmed: 15557667
Signal Transduct Target Ther. 2017;2:
pubmed: 29158945
Nat Immunol. 2008 Apr;9(4):353-9
pubmed: 18349815
PLoS Pathog. 2010 Nov 04;6(11):e1001179
pubmed: 21079691
Invest Ophthalmol Vis Sci. 2011 Jul 29;52(8):6012-7
pubmed: 21693601
Front Immunol. 2019 Mar 01;10:356
pubmed: 30881362
PLoS Negl Trop Dis. 2008 Jul 16;2(7):e264
pubmed: 18628987
Nat Rev Dis Primers. 2022 May 26;8(1):32
pubmed: 35618795
Infect Immun. 1997 Mar;65(3):1003-6
pubmed: 9038309
Infect Immun. 2011 Jul;79(7):2928-35
pubmed: 21536799
Proteomics Clin Appl. 2015 Feb;9(1-2):169-86
pubmed: 25488355
Infect Immun. 1996 Aug;64(8):3273-9
pubmed: 8757864
Cell Death Dis. 2022 Jan 12;13(1):53
pubmed: 35022393
PLoS Negl Trop Dis. 2016 Aug 02;10(8):e0004859
pubmed: 27483002
Arch Ophthalmol. 1983 Apr;101(4):634-5
pubmed: 6838425
Infect Immun. 2011 Dec;79(12):4977-83
pubmed: 21911461
Infect Immun. 2010 Nov;78(11):4895-911
pubmed: 20823212
Front Immunol. 2019 May 31;10:1178
pubmed: 31231369
Nat Rev Immunol. 2020 Jun;20(6):375-388
pubmed: 32132681
Cell Microbiol. 2019 Apr;21(4):e12993
pubmed: 30551267
Nat Commun. 2017 Apr 25;8:15013
pubmed: 28440293
Immunol Rev. 2009 Jan;227(1):248-63
pubmed: 19120489
Prog Retin Eye Res. 2012 Nov;31(6):527-50
pubmed: 22732126
PLoS Negl Trop Dis. 2019 Aug 14;13(8):e0007638
pubmed: 31412025
Front Immunol. 2021 Nov 08;12:717311
pubmed: 34819931
PLoS Med. 2006 Aug;3(8):e266
pubmed: 16881731
Clin Exp Immunol. 2005 Nov;142(2):347-53
pubmed: 16232223
BMC Med Genet. 2009 Dec 16;10:138
pubmed: 20015396
Biochem Cell Biol. 2017 Feb;95(1):34-40
pubmed: 28094551
PLoS Negl Trop Dis. 2013 Jul 25;7(7):e2347
pubmed: 23936573
BMC Bioinformatics. 2008 Dec 29;9:559
pubmed: 19114008
FEMS Immunol Med Microbiol. 2010 Jun 1;59(1):108-16
pubmed: 20370824
Exp Eye Res. 2006 May;82(5):885-98
pubmed: 16309672
J Microbiol Methods. 2017 Aug;139:95-102
pubmed: 28487054
Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):2216-2221
pubmed: 29440378
J Immunol. 2005 Jul 1;175(1):450-60
pubmed: 15972679