Expression of TLR 2, TLR 4 and iNOS in Cervical Monocytes of Chlamydia trachomatis-infected Women and Their Role in Host Immune Response

Agrawal, Tanvi; Bhengraj, Apurb Rashmi; Vats, Vikas; Salhan, Sudha; Mittal, Aliza

doi:10.1111/j.1600-0897.2011.01064.x

Cited by 28 publications

(21 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The antimicrobial potential of NO during chlamydial infection in humans and mice appears to be variable (15,16,46). Furthermore, innate immunity against Chlamydia in human epithelial cells is predominantly mediated by the induction of the IDO that starves Chlamydia of the essential nutrient tryptophan (47), whereas in human macrophages the induction of iNOS has been found to be the first line of defense against chlamydial infection (48).…”

Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatisInhibits Inducible NO Synthase in Human Mesenchymal Stem Cells by Stimulating Polyamine Synthesis

Abu-Lubad

Meyer

Al‐Zeer

2014

The Journal of Immunology

View full text Add to dashboard Cite

Chlamydia trachomatis is considered the most common agent of sexually transmitted disease worldwide. As an obligate intracellular bacterium, it relies on the host for survival. Production of NO is an effective antimicrobial defense mechanism of the innate immune system. However, whether NO is able to arrest chlamydial growth remains unclear. Similarly, little is known about the mechanisms underlying subversion of cellular innate immunity by C. trachomatis. By analyzing protein and mRNA expression in infected human mesenchymal stem cells, combined with RNA interference and biochemical assays, we observed that infection with C. trachomatis led to downregulated expression of inducible NO synthase (iNOS) in human mesenchymal stem cells in vitro. Furthermore, infection upregulated the expression of the rate-limiting enzyme in the polyamine biosynthetic pathway, ornithine decarboxylase, diverting the iNOS substrate l-arginine toward the synthesis of polyamines. Inhibition of ornithine decarboxylase activity using small interfering RNA or the competitive inhibitor difluoromethylornithine restored iNOS protein expression and activity in infected cells and inhibited chlamydial growth. This inhibition was mediated through tyrosine nitration of chlamydial protein by peroxynitrite, an NO metabolite. Thus, Chlamydia evades innate immunity by inhibiting NO production through induction of the alternative polyamine pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatisInhibits Inducible NO Synthase in Human Mesenchymal Stem Cells by Stimulating Polyamine Synthesis

Abu-Lubad

Meyer

Al‐Zeer

2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Flow cytometric analysis of lymphocytes present at the cervixes of C. trachomatis-infected women identified the increased presence of a unique cell type, ␣4␤7 ϩ CLA ϩ memory T cells (51). Stimulation of cervical monocytes with chlamydial EBs showed increased expression of Toll-like receptor 2 (TLR2) and TLR4, and both receptors were also found to be expressed at higher levels in cervical cells from infected women than in those from uninfected women (52). The levels of IL-1␤, IL-4, IL-5, IL-6, and IL-10 were reported to be significantly higher in enriched cervical T cells stimulated with chlamydial inclusion (Inc) membrane proteins from women with C. trachomatis-related infertility (n ϭ 18) than in those from C. trachomatis-positive fertile women (n ϭ 14) (53).…”

Section: Immune Responses From Reproductive Sites and Tissuesmentioning

confidence: 99%

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

et al. 2015

View full text Add to dashboard Cite

SUMMARY Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen worldwide. Infection can result in serious reproductive pathologies, including pelvic inflammatory disease, ectopic pregnancy, and infertility, in women. However, the processes that result in these reproductive pathologies have not been well defined. Here we review the evidence for the human disease burden of these chlamydial reproductive pathologies. We then review human-based evidence that links Chlamydia with reproductive pathologies in women. We present data supporting the idea that host, immunological, epidemiological, and pathogen factors may all contribute to the development of infertility. Specifically, we review the existing evidence that host and pathogen genotypes, host hormone status, age of sexual debut, sexual behavior, coinfections, and repeat infections are all likely to be contributory factors in development of infertility. Pathogen factors such as infectious burden, treatment failure, and tissue tropisms or ascension capacity are also potential contributory factors. We present four possible processes of pathology development and how these processes are supported by the published data. We highlight the limitations of the evidence and propose future studies that could improve our understanding of how chlamydial infertility in women occurs and possible future interventions to reduce this disease burden.

show abstract

“…C. trachomatis is able to avoid destruction by preventing lysosomal fusion and replicating in an inclusion outside the endocytic pathway (18). Scarring associated with C. trachomatis infections may be the result of increased production of inducible nitric oxide synthase (iNOS) and mediators such as activins (20,21).…”

Section: Chlamydia Biologymentioning

confidence: 99%

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

Vasilevsky¹,

Greub

Nardelli-Haefliger

et al. 2014

Clin Microbiol Rev

View full text Add to dashboard Cite

SUMMARY Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide, and despite significant advances in chlamydial research, a prophylactic vaccine has yet to be developed. This Gram-negative obligate intracellular bacterium, which often causes asymptomatic infection, may cause pelvic inflammatory disease (PID), ectopic pregnancies, scarring of the fallopian tubes, miscarriage, and infertility when left untreated. In the genital tract, Chlamydia trachomatis infects primarily epithelial cells and requires Th1 immunity for optimal clearance. This review first focuses on the immune cells important in a chlamydial infection. Second, we summarize the research and challenges associated with developing a chlamydial vaccine that elicits a protective Th1-mediated immune response without inducing adverse immunopathologies.

show abstract

Expression of TLR 2, TLR 4 and iNOS in Cervical Monocytes of Chlamydia trachomatis-infected Women and Their Role in Host Immune Response

Cited by 28 publications

References 42 publications

Chlamydia trachomatisInhibits Inducible NO Synthase in Human Mesenchymal Stem Cells by Stimulating Polyamine Synthesis

Chlamydia trachomatisInhibits Inducible NO Synthase in Human Mesenchymal Stem Cells by Stimulating Polyamine Synthesis

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

Contact Info

Product

Resources

About