+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Interruption of CXCL13-CXCR5 axis increases upper genital tract pathology and activation of NKT cells following chlamydial genital infection



Interruption of CXCL13-CXCR5 axis increases upper genital tract pathology and activation of NKT cells following chlamydial genital infection



Plos One 7(11): E47487



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. 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-IFNγ, CD4-IL-17, CD4-IL-10 & CD8-TNFα) in the oviducts. NKT cell depletion in vitro reduced IL-17α 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). 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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053927545

Download citation: RISBibTeXText

PMID: 23189125

DOI: 10.1371/journal.pone.0047487


Related references

Intranasal Chlamydial proteaselike activity factor immunization enhances protective immunity and reduces upper genital tract pathology following genital Chlamydia muridarum challenge. 2006

Cell-mediated immune responses in the genital tract and genital-associated lymph nodes to murine chlamydial genital infection. Abstracts of the General Meeting of the American Society for Microbiology 95(0): 277, 1995

Rectal administration of a chlamydial subunit vaccine protects against genital infection and upper reproductive tract pathology in mice. Plos One 12(6): E0178537, 2017

Susceptibility to reinfection after a primary chlamydial genital infection is associated with a decrease of antigen-specific T cells in the genital tract. Infection and Immunity 59(4): 1346-1351, 1991

Chlamydial variants differ in ability to ascend the genital tract in the guinea pig model of chlamydial genital infection. Infection and Immunity 83(8): 3176-3183, 2015

CD8⁺CXCR5⁺ T cells regulate pathology in the genital tract. Infectious Diseases in Obstetrics and Gynecology 2013: 813238, 2013

Influence of the estrous cycle on the development of upper genital tract pathology as a result of chlamydial infection in the guinea pig model of pelvic inflammatory disease. American Journal of Pathology 142(4): 1291-1296, 1993

Chlamydial genital tract infections. Experimental infection of the primate genital tract with Chlamydia trachomatis. American Journal of Pathology 106(1): 132-135, 1982

Protective efficacy of a parenterally administered MOMP-derived synthetic oligopeptide vaccine in a murine model of Chlamydia trachomatis genital tract infection: Serum neutralizing IgG antibodies do not protect against chlamydial genital tract infection. Vaccine 13(11): 1023-1032, 1995

Tumor Necrosis Factor (TNF) Receptor Superfamily Member 1b on CD8+ T Cells and TNF Receptor Superfamily Member 1a on Non-CD8+ T Cells Contribute Significantly to Upper Genital Tract Pathology Following Chlamydial Infection. Journal of Infectious Diseases 211(12): 2014-2022, 2015

Male genital tract chlamydial infection: implications for pathology and infertility. Biology of Reproduction 79(2): 180-189, 2008

Characterization of lymphocyte response in the female genital tract during ascending Chlamydial genital infection in the guinea pig model. Infection and Immunity 68(9): 5293-5298, 2000

Silent upper genital tract chlamydial infection and disease in women. International Journal of Std and Aids 8(5): 329-331, 1997

Identification of novel markers for uncomplicated lower genital tract infections and upper genital tract pathology due to Chlamydia trachomatis. International Journal of Infectious Diseases 15(4): E257-E266, 2011

Infertility as a consequence of chlamydial infection of the upper genital tract in female mice. Sexually Transmitted Diseases 11(2): 64-67, 1984