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A Human Fallopian Tube Model for Investigation of C. trachomatis Infections
Published on: August 11, 2012
IL-6-mediated signaling pathways limit Chlamydia muridarum infection and exacerbate its pathogenicity in the mouse
Xin Sun1, Qi Tian1, Luying Wang2
1Department of Obstetrics and Gynecology, 3rd Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Abstract:
Chlamydia muridarum induction of mouse hydrosalpinx, depending on both tubal infection and inflammation, has been used for investigating Chlamydia trachomatis pathogenesis. We now report that IL-6 both inhibits C. muridarum infection and exacerbates pathogenicity in the mouse genital tract. When intravaginally inoculated with a high dose of C. muridarum, IL-6-deficient mice developed more extensive genital tract infection with severe hydrosalpinx, suggesting that IL-6 is required for controlling the high dose infection but not essential for C. muridarum-induced pathology. However, at a low dose, IL-6-deficient mice still developed more extensive infection in the genital tract but no longer with significant pathology, suggesting that IL-6 is required for both controlling the low dose infection and exacerbating the low dose infection-induced pathology. The lack of hydrosalpinx in IL-6-deficient mice correlated with significantly reduced inflammatory infiltration in the oviduct tissue and decreased spleen CD4+ and CD8+ T cells that produce TNFα. Thus, IL-6-dependent pathways are important for both limiting chlamydial colonization in the genital tract mucosal tissues regardless of the infection doses and exacerbating chlamydial pathogenicity in the upper genital tract when IL-6-independent pathogenic mechanisms are not yet activated with a low infection dose.
Insights
Interleukin-6 (IL-6) plays a dual role in Chlamydia muridarum genital tract infections. While IL-6 limits infection, it also exacerbates pathology, particularly at lower doses, impacting hydrosalpinx development.
Area of Science:
- Immunology
- Microbiology
- Reproductive Health
Background:
- Chlamydia muridarum mouse model is used to study Chlamydia trachomatis pathogenesis.
- Hydrosalpinx development depends on tubal infection and inflammation.
Purpose of the Study:
- To investigate the role of Interleukin-6 (IL-6) in Chlamydia muridarum infection and pathogenesis.
- To understand IL-6's influence on genital tract infection and hydrosalpinx development.
Main Methods:
- Intravaginal inoculation of mice with varying doses of C. muridarum.
- Comparison of infection and pathology in wild-type versus IL-6-deficient mice.
- Analysis of inflammatory infiltration and T cell responses (TNFα production).
Main Results:
- IL-6-deficient mice showed more extensive genital tract infection with severe hydrosalpinx at high doses.
- At low doses, IL-6-deficient mice had extensive infection but reduced pathology.
- Reduced hydrosalpinx in IL-6-deficient mice correlated with decreased inflammation and TNFα-producing T cells.
Conclusions:
- IL-6 is crucial for controlling C. muridarum infection regardless of dose.
- IL-6 exacerbates C. muridarum-induced pathology, especially at low infection doses.
- IL-6-dependent pathways influence both chlamydial colonization and disease severity in the mouse genital tract.
