TLR9 KO mice, haplotypes and CPG indices in Chlamydia trachomatis infection.

نویسندگان

  • S Ouburg
  • J M Lyons
  • J A Land
  • J E den Hartog
  • J S A Fennema
  • H J C de Vries
  • C A Bruggeman
  • J I Ito
  • A S Peña
  • P S J Lundberg
  • S A Morré
چکیده

Previous studies have investigated the role of Toll-like receptor (TLR)2 and TLR4 in susceptibility to and severity of Chlamydia trachomatis infections. In this study we employ a unique integrated approach to study the role of the intracellular CpG DNA receptor: we use a murine knockout (KO) model to assess TLR9 relevance, study human TLR9 genotypes and haplotypes in sexually transmitted disease (STD) patients and subfertile women with or without tubal pathology and use in silico TLR9 CpG index calculations to assess potential immunostimulatory properties of the Chlamydia bacterium. Although no significant differences in the course of initial infections were observed between KO mice and wild-type mice the TLR9 KO mice showed a significant level of protection upon reinfection (P = 0.02). We did not observe significant differences in genotype frequencies between C. trachomatis-positive and C. trachomatisnegative women (STD patients). However, haplotype analyses revealed a trend between C. trachomatis-positive and C. trachomatis-negative women in the carriage of haplotype IV (P = 0.061; OR: 2.6; 95% CI: 1.0-6.8). In women with subfertility, odds ratios between 2 and 3 were found for tubal pathology risk, but they did not reach significance due to cohort size limitations. Finally, CpG sequence analysis showed mildly immunostimulatory properties for the genomic sequences of Chlamydia serovars B and D. Based on the murine model, human immunogenetic studies and in silico CpG index analyses, TLR9 seems to play a modest role in C. trachomatis infections. Extension of the human cohorts is necessary to significantly prove the effect in humans.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

TLR2, TLR4 and TLR9 genotypes and haplotypes in the susceptibility to and clinical course of Chlamydia trachomatis infections in Dutch women.

Chlamydia trachomatis infections demonstrate remarkable differences in clinical course that are approximately 40% based on host genetic variation. Here, we study the single nucleotide polymorphisms (SNPs) and their haplotypes in TLR2, TLR4 and TLR9 (TLR2 +2477G>A; TLR2 -16934T>A; TLR4+896A>G; TLR9 -1237T>C and TLR9 +2848G>A) in relation to the susceptibility to, and severity of C. trachomatis i...

متن کامل

Chapter 4 TLR2, TLR4, and TLR9 haplotypes in the susceptibility to and severity of Chlamydia trachomatis infections in Dutch women

Chlamydia trachomatis (Ct) infections have remarkable interindividual differences in the clinical course which are for 40% based on host genetic variation including genes encoding immunoregulatory and bacteria sensing proteins. As patient-related immunomodulating factors, toll-like receptors (TLRs) are closely involved in pathogen recognition and host defence in Ct infections. Here we study the...

متن کامل

Immunization with the Chlamydia trachomatis mouse pneumonitis major outer membrane protein by use of CpG oligodeoxynucleotides as an adjuvant induces a protective immune response against an intranasal chlamydial challenge.

Recently, we have shown that a vaccine consisting of a purified preparation of the Chlamydia trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP) and Freund's adjuvant can protect mice against a genital challenge. Here, we wanted to determine if CpG motifs could be used as an immune modulator to the MOMP to induce protection in mice against an intranasal (i.n.) challenge. On...

متن کامل

O-28: New Insights into the Mechanisms UnderlyingChlamydia Trachomatis Infection InducedFemale Infertility

Background: Chlamydia (C.) trachomatis is an obligate intracellular gram-negative pathogen affecting over 600 million people worldwide with 92 million new cases occurring globally each year. Genital C. trachomatis infection has been recognized as the most common cause of pelvic inflammatory disease leading to severe tubal damage, ectopic pregnancy, hydrosalpinx and infertility. However, the mec...

متن کامل

P-59: Chlamydia Trachomatis Infection in Femaleswith Secondary Infertility

Background: We designed a prospective study to assess the role of Chlamydia in secondary infertility Materials and Methods: 40 women with secondary infertility and 30 term healthy pregnant women of similar age composition were studied for past and present chlamydia trachomatis infection. Women attending the outpatient department of Obstetrics and Gynaecology with complaint of secondary infertil...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Drugs of today

دوره 45 Suppl B  شماره 

صفحات  -

تاریخ انتشار 2009