Interruption of CXCL13-CXCR5 Axis Increases Upper Genital Tract Pathology and Activation of NKT Cells following Chlamydial Genital Infection
| Autor: | Jolande A. Land, Amanda Freed, Guangchao Liu, Sander Ouburg, Heljä-Marja Surcel, Janina Jiang, Servaas A. Morré, Jolein Pleijster, Nora Rozengurt, Jorma Paavonen, Aila Tiitinen, Archana Khurana, Cheryl I. Champion, Kathleen A. Kelly, Ouafae Karimi, Mitchell Kronenberg |
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| Přispěvatelé: | Reproductive Origins of Adult Health and Disease (ROAHD), Clinicum, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, Medical Microbiology and Infection Prevention, CCA - Immuno-pathogenesis, RS: CAPHRI School for Public Health and Primary Care, RS: GROW - School for Oncology and Reproduction, Gynaecologie en Obstetrie, Institute for Public Health Genomics |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Pathology
Chemokine SUBSETS MURIDARUM INFECTION medicine.disease_cause Lymphocyte Activation Reproductive Tract Infections Cohort Studies Mice 0302 clinical medicine 3123 Gynaecology and paediatrics T-Lymphocyte Subsets Pelvic inflammatory disease TRACHOMATIS INFECTION IMMUNE-RESPONSE Chlamydia Immune Response 0303 health sciences Multidisciplinary biology Natural killer T cell CD1D 3. Good health Bacterial Pathogens medicine.anatomical_structure Infectious Diseases Chemokine secretion Medicine Cytokines Female Research Article EXPRESSION Receptors CXCR5 medicine.medical_specialty Chlamydia muridarum T cell Science education Immunology Sexually Transmitted Diseases Immunopathology Microbiology Polymorphism Single Nucleotide White People 03 medical and health sciences medicine ANTIGEN PRESENTATION Genetics Animals Humans Biology 030304 developmental biology Inflammation KILLER T-CELLS Immunity Human Genetics Reproductive Immunology PELVIC INFLAMMATORY DISEASE Immunologic Subspecialties Chlamydia Infections biology.organism_classification medicine.disease Chemokine CXCL13 Disease Models Animal biology.protein Natural Killer T-Cells Antigens CD1d Chlamydia trachomatis 030215 immunology |
| Zdroj: | PLoS ONE PLoS ONE, 7(11):e47487. PUBLIC LIBRARY SCIENCE Jiang, J, Karimi, O, Ouburg, S, Champion, C I, Khurana, A, Liu, G C, Freed, A, Pleijster, J, Rozengurt, N, Land, J A, Surcel, H M, Tiitinen, A, Paavonen, J, Kronenberg, M, Morre, S A & Kelly, K A 2012, ' Interruption of CXCL13-CXCR5 Axis Increases Upper Genital Tract Pathology and Activation of NKT Cells following Chlamydial Genital Infection ', PLoS ONE, vol. 7, no. 11, e47487 . https://doi.org/10.1371/journal.pone.0047487 PLoS ONE, Vol 7, Iss 11, p e47487 (2012) PLoS ONE, 7(11):e47487. Public Library of Science PLOS ONE, 7(11):e7487. Public Library of Science |
| ISSN: | 1932-6203 |
| Popis: | Background: Regulation of immune responses is critical for controlling inflammation and disruption of this process can lead to tissue damage. We reported that CXCL13 was induced in fallopian tube tissue following C. trachomatis infection. Here, we examined the influence of the CXCL13-CXCR5 axis in chlamydial genital infection.Methodology and Principal Findings: Disruption of the CXCL13-CXCR5 axis by injecting anti-CXCL13 Ab to BALB/c mice or using Cxcr5-/- mice increased chronic inflammation in the upper genital tract (UGT; uterine horns and oviducts) after Chlamydia muridarum genital infection (GT). Further studies in Cxcr5-/- mice showed an elevation in bacterial burden in the GT and increased numbers of neutrophils, activated DCs and activated NKT cells early after infection. After resolution, we noted increased fibrosis and the accumulation of a variety of T cells subsets (CD4-IFN gamma, CD4-IL-17, CD4-IL-10 & CD8-TNF alpha) in the oviducts. NKT cell depletion in vitro reduced IL-17 alpha and various cytokines and chemokines, suggesting that activated NKT cells modulate neutrophils and DCs through cytokine/chemokine secretion. Further, chlamydial glycolipids directly activated two distinct types of NKT cell hybridomas in a cell-free CD1d presentation assay and genital infection of Cd1d-/- mice showed reduced oviduct inflammation compared to WT mice. CXCR5 involvement in pathology was also noted using single-nucleotide polymorphism analysis in C. trachomatis infected women attending a sub-fertility clinic. Women who developed tubal pathology after a C. trachomatis infection had a decrease in the frequency of CXCR5 SNP +10950 T>C (rs3922).Conclusions/Significance: These experiments indicate that disruption of the CXCL13-CXCR5 axis permits increased activation of NKT cells by type I and type II glycolipids of Chlamydia muridarum and results in UGT pathology potentially through increased numbers of neutrophils and T cell subsets associated with UGT pathology. In addition, CXCR5 appears to contribute to inter-individual differences in human tubal pathology following C. trachomatis infection. |
| Databáze: | OpenAIRE |
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