Association of CCR5, TLR2, TLR4 and MBL genetic variations with genital tract infections and tubal factor infertility

Laisk, Triin; Peters, Maire; Saare, Merli; Haller-Kikkatalo, Kadri; Karro, Helle; Salumets, Andres

doi:10.1016/j.jri.2010.06.001

Cited by 24 publications

(30 citation statements)

References 44 publications

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“…However, in haplotype analysis, they showed that haplotype TG was protective for developing tubal pathology. Laisk et al [21] also evaluated the role of TLR2 +2477G>A (rs5743708) in developing tubal pathology and found no association, confirming the results of the single SNP analyses of Karimi et al [19]. …”

Section: Pattern Recognition Receptorssupporting

confidence: 57%

“…Barr et al [26] demonstrated that this mutation has a protective effect against developing tubal pathology when both alleles are mutated. However, these results were not confirmed in a recent study [21]. For this inconsistency, the authors suggest that the ligand of CCR5, RANTES (CCL5), binds the CCR1 chemokine receptor as well, therefore inducing a normal response.…”

Section: Pattern Recognition Receptorsmentioning

confidence: 80%

“…Results of this study are highly specific, but have low sensitivity, since not all women with tubal pathology had this combination of C. trachomatis and cHSP60 serology, and TLR4 +896 mutation carriage. Laisk et al [21] also investigated the role of this SNP in developing tubal pathology; they did not find any association. Taylor et al [23] studied a different TLR4 polymorphism, rs1927911, and found that the mutant genotype increases the susceptibility to C. trachomatis infections.…”

Section: Pattern Recognition Receptorsmentioning

confidence: 99%

See 2 more Smart Citations

Chlamydia trachomatis Infections and Subfertility: Opportunities to Translate Host Pathogen Genomic Data into Public Health

Lal¹,

Malogajski²,

Verweij

et al. 2013

Public Health Genomics

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Chlamydia trachomatis (CT) infections in women can result in tubal pathology (TP). Worldwide 10-15% of all couples are subfertile, meaning they did not get pregnant after 1 year. Part of the routine subfertility diagnostics is the Chlamydia Antibody Test (CAT) to decide for laparoscopy or not in order to diagnose TP. The CAT positive and negative predictive value is such that many unneeded laparoscopies are done and many TP cases are missed. Addition of host genetic markers related to infection susceptibility and severity could potentially improve the clinical management of couples who suffer from subfertility. In the present study, the potential translational and clinical value of adding diagnostic host genetic marker profiles on the basis of infection and inflammation to the current clinical management of subfertility was investigated. This review provides an overview of the current state of the art of host genetic markers in relation to CT infection, proposes a new clinical diagnostic approach, and investigates how the Learning-Adapting-Leveling model (LAL, a public health genomic (PHG) model) can be of value and provide insight to see whether these host genetic markers can be translated into public health. This review shows that the preliminary basis of adding host genetic marker profiles to the current diagnostic procedures of subfertility is present but has to be further developed before implementation into health care can be achieved. CT infection is an example in the field of PHG with potential diagnostic to be taken up in the future in the field of subfertility diagnosis with a time line for integration to be dependent on enhanced participation of many stakeholders in the field of PHG which could be advanced through the LAL model.

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Section: Pattern Recognition Receptorssupporting

confidence: 57%

Section: Pattern Recognition Receptorsmentioning

confidence: 80%

Section: Pattern Recognition Receptorsmentioning

confidence: 99%

See 1 more Smart Citation

Chlamydia trachomatis Infections and Subfertility: Opportunities to Translate Host Pathogen Genomic Data into Public Health

Lal¹,

Malogajski²,

Verweij

et al. 2013

Public Health Genomics

View full text Add to dashboard Cite

show abstract

“…It is possible that TLR2 signaling pathways play a more significant role in C. trachomatis infection in humans. However, the TLR2 genotype was not associated with tubal infertility in women (44). Thus, more investigations are required to address the precise role of TLR2 signaling pathways in human chlamydial infection and pathogenesis.…”

Section: Figmentioning

confidence: 99%

Signaling via Tumor Necrosis Factor Receptor 1 but Not Toll-Like Receptor 2 Contributes Significantly to Hydrosalpinx Development following Chlamydia muridarum Infection

et al. 2014

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Chlamydial infection in the lower genital tract can lead to hydrosalpinx, which is accompanied by activation of both pattern recognition receptor TLR2-and inflammatory cytokine receptor TNFR1-mediated signaling pathways. In the current study, we compared the relative contributions of these two receptors to chlamydial induction of hydrosalpinx in mice. We found that mice with or without deficiencies in TLR2 or TNFR1 displayed similar time courses of live organism shedding from vaginal swabs, suggesting that these receptor-mediated signaling pathways are not required for controlling chlamydial lower genital infection. However, mice deficient in TNFR1 but not TLR2 developed significantly reduced hydrosalpinx. The decreased pathogenicity correlated with a significant reduction in interleukin-17 by in vitro-restimulated splenocytes of TNFR1-deficient mice. Although TLR2-deficient mice developed hydrosalpinx as severe as that of wild-type mice, peritoneal macrophages from mice deficient in TLR2 but not TNFR1 produced significantly reduced cytokines upon chlamydial stimulation, suggesting that reduced macrophage responses to chlamydial infection do not always lead to a reduction in hydrosalpinx. Thus, we have demonstrated that the signaling pathways triggered by the cytokine receptor TNFR1 play a more significant role in chlamydial induction of hydrosalpinx than those mediated by the pattern recognition receptor TLR2, which has laid a foundation for further revealing the chlamydial pathogenic mechanisms.

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“…Ten TLRs have been identified in the human body, and TLR1 to TLR4 are expressed in the female genital tract (109). TLR2 and TLR4 are also expressed on various cells (110). In a prospective genotypic study with female patients attending a sexual health clinic and a fertility clinic in Amsterdam, Netherlands, Karimi et al (111) demonstrated a possible protective role for a TLR2 haplotype.…”

Section: Human Genotypic Factors Associated With C Trachomatis Infermentioning

confidence: 99%

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

et al. 2015

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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.

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Association of CCR5, TLR2, TLR4 and MBL genetic variations with genital tract infections and tubal factor infertility

Cited by 24 publications

References 44 publications

<b><i>Chlamydia trachomatis</i></b> Infections and Subfertility: Opportunities to Translate Host Pathogen Genomic Data into Public Health

<b><i>Chlamydia trachomatis</i></b> Infections and Subfertility: Opportunities to Translate Host Pathogen Genomic Data into Public Health

Signaling via Tumor Necrosis Factor Receptor 1 but Not Toll-Like Receptor 2 Contributes Significantly to Hydrosalpinx Development following Chlamydia muridarum Infection

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

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