TLR2,TLR4andTLR9genotypes and haplotypes in the susceptibility to and clinical course ofChlamydia trachomatisinfections in Dutch women

Verweij, Stephan P.; Karimi, Ouafae; Pleijster, Jolein; Lyons, Joseph M.; Vries, Henry J. C. de; Land, Jolande A.; Morré, Servaas A.; Ouburg, Sander

doi:10.1093/femspd/ftv107

Cited by 13 publications

(18 citation statements)

References 46 publications

(46 reference statements)

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“…Genital chlamydia infection, a disease caused by infection with C. trachomatis , is the most frequently reported bacterial STD in the United States 1,2 . We still do not fully understand why some women are more likely to develop an asymptomatic infection, have severe infection leading to PID and tubal factor infertility, or after exposure to C. trachomatis stay uninfected 3,6,7 . We hypothesize that some of these differences amongst individuals infected with C. trachomatis might be due to the time of day they were exposed to it.…”

Section: Discussionmentioning

confidence: 99%

“…Women who are infected with C. trachomatis have a greater chance of becoming infertile 6,7 . Reinfection leads to increased pathology and infertility, here we used mice that were reinfected with C. muridarum to determine the effect of time of day of chlamydia infection on fertility outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…There are varying levels of severity among women who do develop complications such as cervicitis, PID, uterine fibrosis and tubal factor infertility (TFI) regardless of how many times they have been exposed or have become reinfected 4,5 . A better understanding of how some women develop genital disease (PID alone, PID with Salpingitis, TFI or are asymptomatic) following chlamydia infection, while others do not, and the underlying mechanisms 6,7 will enhance a search for prevention measures.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Time of Day of Infection on Chlamydia Infectivity and Pathogenesis

Lundy

Ahmad

Simoneaux

et al. 2019

Sci Rep

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Genital chlamydia infection in women causes complications such as pelvic inflammatory disease and tubal factor infertility, but it is unclear why some women are more susceptible than others. Possible factors, such as time of day of chlamydia infection on chlamydial pathogenesis has not been determined. We hypothesised that infections during the day, will cause increased complications compared to infections at night. Mice placed under normal 12:12 light: dark (LD) cycle were infected intravaginally with Chlamydia muridarum either at zeitgeber time 3, ZT3 and ZT15. Infectivity was monitored by periodic vaginal swabs and chlamydiae isolation. Blood and vaginal washes were collected for host immunologic response assessments. The reproductive tracts of the mice were examined histopathologically, and fertility was determined by embryo enumeration after mating. Mice infected at ZT3 shed significantly more C. muridarum than mice infected at ZT15. This correlated with the increased genital tract pathology observed in mice infected at ZT3. Mice infected at ZT3 were less fertile than mice infected at ZT15. The results suggest that the time of day of infection influences chlamydial pathogenesis, it indicates a possible association between complications from chlamydia infection and host circadian clock, which may lead to a better understanding of chlamydial pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Time of Day of Infection on Chlamydia Infectivity and Pathogenesis

Lundy

Ahmad

Simoneaux

et al. 2019

Sci Rep

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“…However, if the upregulated immune system is unable to clear the infection, it might be stimulated too much, resulting in enhanced inflammation and tissue damage and thus increasing the chance of episodes of PID and potentially subsequent tubal scarring. The absence of an association between susceptibility and TLR2 + 2477 G > A could be explained by earlier studies, which found it only associated with haplotype combinations [ 14 ]. The haplotypes with an increased risk of infection were heterozygous (GA) or homozygous (GG) for +2477 SNP [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…It has also been shown to be important in the early production of inflammatory mediators and the development of chronic inflammatory pathology [ 13 ]. Verweij et al found that TLR2 + 2477 *A provided an increased risk for the development of tubal pathology in CT positive women (OR 17.5) [ 14 ], although the study group was rather small. CT seropositive women carrying the NOD1 GG insertion had a more than double increased risk of tubal pathology (OR: 2.25; 95%CI: 1.08–4.67, p = 0.04) [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Can Previous Associations of Single Nucleotide Polymorphisms in the TLR2, NOD1, CXCR5, and IL10 Genes in the Susceptibility to and Severity of Chlamydia trachomatis Infections Be Confirmed?

et al. 2021

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Clear inter-individual differences exist in the response to C. trachomatis (CT) infections and reproductive tract complications in women. Host genetic variation like single nucleotide polymorphisms (SNPs) have been associated with differences in response to CT infection, and SNPs might be used as a genetic component in a tubal-pathology predicting algorithm. Our aim was to confirm the role of four genes by investigating proven associated SNPs in the susceptibility and severity of a CT infection. A total of 1201 women from five cohorts were genotyped and analyzed for TLR2 + 2477 G > A, NOD1 + 32656 T −> GG, CXCR5 + 10950 T > C, and IL10 − 1082 A > G. Results confirmed that NOD1 + 32656 T −>GG was associated with an increased risk of a symptomatic CT infection (OR: 1.9, 95%CI: 1.1–3.4, p = 0.02), but we did not observe an association with late complications. IL10 − 1082 A > G appeared to increase the risk of late complications (i.e., ectopic pregnancy/tubal factor infertility) following a CT infection (OR = 2.8, 95%CI: 1.1–7.1, p = 0.02). Other associations were not found. Confirmatory studies are important, and large cohorts are warranted to further investigate SNPs’ role in the susceptibility and severity of a CT infection.

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