Abstract
Objective: The relationship between a single nucleotide polymorphism (TLR4 896 A>G) in the toll-like
receptor-4 (TLR4) gene, qualitative and quantitative changes in vaginal micro-flora
and vaginal interleukin (IL)-1β and IL-1 receptor antagonist (IL-1ra) concentrations
in pregnant women were evaluated. Study design: Qualitative and quantitative microbial methods were used to characterize vaginal
micro-flora of 238 women at 18–22 weeks gestation. Polymerase chain reaction was used
to determine TLR4 genotype. IL-1β and IL-1ra concentrations in vaginal lavage samples
were measured by ELISA. Results: The TLR4 variant was identified in 10.3% of women. Carriage of this variant was associated
with a median increase in vaginal pH (P=0.05), a greater than 10-fold increase in vaginal Gardnerella vaginalis levels (P<0.0001) and a 10-fold increase in the vaginal concentration of three species of anaerobic
Gram-negative rods, Prevotella, Bacteroides, and Porphyromonas (P=0.08). Colonization with G. vaginalis and/or the anaerobic Gram-negative rods resulted in elevated vaginal IL-1 (P=0.01) and IL-1ra (P<0.0002) concentrations in women who were TLR4 896A homozygotes, but not in TLR4 896G
carriers. Conclusion: The TLR4 896 A>G polymorphism contributes to inter-individual differences in the
vaginal immune defense against G. vaginalis and anaerobic Gram-negative rods.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Obstetrics and Gynecology and Reproductive BiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Quantitative bacteriology of the vaginal flora.J. Infect. Dis. 1977; 136: 271-277
- Methods for quantitative vaginal flora studies.Am. J. Obstet. Gynecol. 1977; 128: 777-781
- Pathogenesis of abnormal vaginal bacterial flora.Am. J. Obstet. Gynecol. 2000; 182: 872-878
- High levels of tumor necrosis factor-alpha and interleukin-1beta in bacterial vaginosis may increase susceptibility to human immunodeficiency virus.J. Infect. Dis. 2000; 182: 467-473
- Relationship of abnormal vaginal flora, proinflammatory cytokines and idiopathic infertility in women undergoing IVF.J. Reprod. Med. 2001; 46: 806-810
- Interleukin 1 receptor antagonist. A new member of the interleukin 1 family.J. Clin. Invest. 1991; 88: 1445-1451
Genç M, Witkin SS, Delaney ML et al. A disproportionate increase in IL-1β over IL-1ra in the cervicovaginal secretions of pregnant women with vaginal infection correlates with preterm birth. Am J Obstet Gynecol 2004;190: in press.
- Innate immune recognition.Annu. Rev. Immunol. 2002; 20: 197-216
- The toll gene of Drosophila, required for dorsal–ventral embryonic polarity, appears to encode a transmembrane protein.Cell. 1988; 52: 269-279
- A human homologue of the Drosophila toll protein signals activation of adaptive immunity.Nature. 1997; 388: 394-397
- Endotoxin signal transduction in macrophages.J. Leukoc. Biol. 1996; 60: 8-26
- Introduction: the role of innate immunity in the adaptive immune response.Semin. Immunol. 1998; 10: 349-350
- TLR4 mutations are associated with endotoxin hyporesponsiveness in humans.Nat. Genet. 2000; 25: 187-191
- The genetics of innate immunity.Chest. 2002; 121: 62S-68S
- Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of Gram-negative infections.J. Infect. Dis. 2002; 186: 1522-1525
- A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease.J. Infect. Dis. 2001; 184: 640-642
- The role that the functional Asp299Gly polymorphism in the toll-like receptor-4 gene plays in susceptibility to Chlamydia trachomatis-associated tubal infertility.J. Infect. Dis. 2003; 187: 341-342
- Role of the toll-like receptor 4 Asp299Gly polymorphism in susceptibility to Candida albicans infection.J. Infect. Dis. 2002; 186: 1377-1378
- Quantitative microbiologic models for preterm delivery.J. Clin. Microbiol. 2003; 41: 1073-1079
- Reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation.J. Clin. Microbiol. 1991; 29: 297-301
- Involvement of class II MHC molecules in the LPS-induction of IL-1/TNF secretions by human monocytes: quantitative differences at the polymorphic level.J. Immunol. 1989; 143: 913-922
- Association between the Asp299Gly polymorphisms in the toll-like receptor 4 and premature births in the Finnish population.Pediatr. Res. 2002; 52: 373-376
- The CARD15 2936insC mutation and TLR4 896 A>G polymorphism in African Americans and risk of preterm premature rupture of membranes (PPROM).Mol. Hum. Reprod. 2002; 8: 1031-1034
- Monocytes heterozygous for the Asp299Gly and Thr399Ile mutations in the toll-like receptor 4 gene show no deficit in lipopolysaccharide signaling.J. Exp. Med. 2003; 197: 1787-1791
Article info
Publication history
Accepted:
February 4,
2004
Received in revised form:
December 19,
2003
Received:
October 10,
2003
Identification
Copyright
© 2004 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.