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Mycoplasma genitalium-encoded MG309 activates NF-kappaB via Toll-like receptors 2 and 6 to elicit proinflammatory cytokine secretion from human genital epithelial cells.

ABSTRACT: Mycoplasma genitalium has been implicated in several important reproductive tract syndromes in women, including pelvic inflammatory disease, cervicitis, and tubal factor infertility. The mechanisms of immune activation are unclear, and we sought to determine whether M. genitalium was capable of activating innate immune responses through ligation of highly expressed Toll-like receptors (TLR) of the genital tract. Using HEK293 cells expressing specific human TLR, viable M. genitalium and the recombinant C-terminal portion of the immunogenic protein MG309 (rMG309c) were shown to activate NF-kappaB via TLR2/6. These data provided a putative mechanism for activation of the innate response in genital tissues. Genital epithelial cells (EC) are the first responders to sexually transmitted pathogens and express high levels of TLR2 and -6. Following exposure to purified rMG309c, vaginal and ecto- and endocervical EC secreted proinflammatory cytokines, including interleukin-6 (IL-6) and IL-8. Vaginal EC were less responsive than cervical EC. The capacity of rMG309c to bind TLR2/6 and elicit inflammation was sensitive to proteinase K digestion and independent of traditional N-terminal lipoylation. Furthermore, the immunostimulatory capacity of rMG309c was localized specifically to a 91-amino-acid subfragment of the recombinant protein, suggesting that TLR activation is likely amino acid based. Together, these data indicated that human vaginal and cervical EC are immunologically responsive to M. genitalium and to purified rMG309c via highly expressed TLR of the genital tract. These findings provide valuable insights into the mechanisms for activation of acute-phase inflammatory responses and suggest that M. genitalium colonization of reproductive tract tissues may result in inflammatory sequelae.

SUBMITTER: McGowin CL

PROVIDER: S-EPMC2643644 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Mycoplasma genitalium-encoded MG309 activates NF-kappaB via Toll-like receptors 2 and 6 to elicit proinflammatory cytokine secretion from human genital epithelial cells.

McGowin Chris L CL Ma Liang L Martin David H DH Pyles Richard B RB

Infection and immunity 20081222 3

Mycoplasma genitalium has been implicated in several important reproductive tract syndromes in women, including pelvic inflammatory disease, cervicitis, and tubal factor infertility. The mechanisms of immune activation are unclear, and we sought to determine whether M. genitalium was capable of activating innate immune responses through ligation of highly expressed Toll-like receptors (TLR) of the genital tract. Using HEK293 cells expressing specific human TLR, viable M. genitalium and the recom ...[more]

PMID: 19103762

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Project description:Background and purposeLactobacilli play a vital role in protecting the vagina against pathogens. Cytokines are vital components of defense against infections in women. The genital mycoplasmas, Mycoplasma genitalium and Ureaplasma urealyticum, are associated with various infectious diseases in adults and infants. The objective of our study is to identify differences in cytokine profile and Lactobacillus species dominance between a study group of non-pregnant pre-menopausal women with genital M. genitalium or U. urealyticum colonization and a control group of non-pregnant pre-menopausal women without genital M. genitalium or U. urealyticum colonization.MethodsA real-time polymerase chain reaction was performed to measure Lactobacillus species in vaginal swab samples. Cytokine analysis was performed using multiplex immunoassay techniques. Analysis of variance confirmed a significant difference in cytokine profiles between patient groups, with t-tests identifying the most significantly different cytokines. Categorical data analysis identified significant patterns of relative Lactobacillus species dominance in the study group.ResultsLactobacillus iners was the predominant Lactobacillus species in the control group (p = 0.005). There were no dominant Lactobacillus species observed in the study group. Vascular endothelial growth factor A (p = 0.002), interleukin-8 (p = 0.001), and interleukin-1β (p = 0.049) were expressed significantly higher in the study group, whereas interleukin-1 receptor antagonist (p < 0.001), interleukin-10 (p = 0.001), interleukin-12 (p = 0.002), and interferon-γ (p = 0.022) were expressed higher in the control group. Association matrices for cytokines were significantly different between two groups (p < 0.001), with mostly negative associations in the control group and mostly positive associations in the study group.ConclusionCytokine levels, their associations, and the patterns of Lactobacillus species dominance are observed to significantly diverge on the basis of M. genitalium and U. urealyticum colonization among non-pregnant pre-menopausal women.

Dataset Information

Mycoplasma genitalium-encoded MG309 activates NF-kappaB via Toll-like receptors 2 and 6 to elicit proinflammatory cytokine secretion from human genital epithelial cells.

Publications

Mycoplasma genitalium-encoded MG309 activates NF-kappaB via Toll-like receptors 2 and 6 to elicit proinflammatory cytokine secretion from human genital epithelial cells.

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