Secretion of proinflammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis.

Rasmussen, S J; Eckmann, Lars; Quayle, Alison J.; Shen, Li; Zhang, Y X; Anderson, Deborah J.; Fierer, Joshua; Stephens, Richard S.; Kagnoff, Martin F.

doi:10.1172/jci119136

Cited by 468 publications

(440 citation statements)

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“…Our finding suggests a plausible mechanism whereby C. trachomatis infection could be associated with increased risk for cervical cancer, as has been reported in several epidemiological studies. 7,[10][11][12]23,24 It has been reported that C. trachomatis infection may induce large local amounts of pro-inflammatory chemokines, including IL-1, IL-8 and granulocyte-macrophage colony-stimulating factor 25 producing a chronic inflammatory background that may conceivably contribute to HPV DNA persistence in the cervix.…”

Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis infection and persistence of human papillomavirus

Silins

Ryd

Strand

et al. 2005

Intl Journal of Cancer

139

108

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Human papillomavirus (HPV) persistence is the major cause of cervical cancer, but most HPV infections will not persist and risk factors for HPV persistence are not well known. Chlamydia (C.) trachomatis infection seems to also be associated with cervical cancer. We investigated whether C. trachomatis infection is a risk factor for HPV persistence. In a cohort of 12,527 women participating in a population-based HPV screening trial in Sweden, 6,418 women completed testing for HPV DNA by general primer PCR and typing by reverse dot blot hybridization. On average 19 months later, 303 women that had been HPV-positive and had normal cytology at enrollment completed a new HPV test. Environmental exposures were assessed by an 87-item questionnaire. Previous sexually transmitted infections were also investigated by serology. At follow-up, 44% of the women were positive for the same type of HPV DNA as at enrollment. Persistence correlated with length of follow-up (p < 0.01) and condom use seemed to protect against HPV persistence (p < 0.05). The most significant risk factor for persistent presence of HPV DNA was self-reported history of previous C. trachomatis infection (relative risk in multivariate model = 2.09; 95% confidence interval = 1.05-4.18). We conclude that persistence of oncogenic HPV infections is more likely among women with a previous C. trachomatis infection. ' 2005 Wiley-Liss, Inc.Key words: HPV infection; HPV persistence; Chlamydia trachomatis; epidemiology Persistent oncogenic HPV infection is recognized as a necessary factor in development of high grade cervical intraepithelial neoplasia and invasive cervical cancer. 1 Genital infections with oncogenic HPV types are very common among sexually active women, but only a minority of infected women will have a persistent HPV infection. 2-4 Type-specific persistence of HPV (defined as repeated detectability of the same type of HPV DNA in serial samples) is a much stronger risk factor for high-grade CIN 5 and cervical cancer 6 than HPV infection per se.Chlamydia (C.) trachomatis has been found repeatedly to associate with cervical neoplasia and invasive cancer in cross-sectional case-control studies, 7,8 although the association has commonly been thought to be the result of confounding by HPV. During recent years, an association with C. trachomatis has also been found in several biobank-based longitudinal studies with invasive cervical cancer as endpoint. [9][10][11][12] The vexed question of whether the association could be due to confounding by HPV infection is, however, only possible to address in cohort studies comprising only HPV-infected women.A possible explanation for the association of C. trachomatis and cervical cancer might be that the C. trachomatis-induced inflammation results in an impaired ability to clear HPV infections.To investigate these issues, we carried out a prospective, population-based cohort study restricted to HPV-infected women with HPV persistence as the endpoint. Subjects and methods Study settingA population-based randomized mul...

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Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis infection and persistence of human papillomavirus

Silins

Ryd

Strand

et al. 2005

Intl Journal of Cancer

139

108

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“…Shortly after infection is initiated, neutrophils are the most predominant effector cells recruited to the infectious foci (Patton and Kuo, 1989;Kiviat et al, 1990), suggesting that PMNs are involved in controlling the early stages of C. trachomatis infection, and confirmed by a study from Barteneva et al (1996). The acute host response to Chlamydia in the genital tract is primarily initiated and sustained by epithelial cells, the first and main targets of chlamydial infection (Rasmussen et al, 1997;Wyrick et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…IL-8 is one of the most potent C-X-C chemokines and is produced in response to bacterial infection including Chlamydia (Beatty and Sansonetti, 1997;Burns et al, 1997;Rasmussen et al, 1997). Although IL-8 could be detected in culture supernatants of L2-infected HeLa cells as soon as 24 h after infection, the PMN response was detectable only at 36 h after infection.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the lack of detection of IL-1a in HeLa cells infected with C. trachomatis for 12±48 h was expected, at least at the protein level, because this cytokine is mainly released at the end of the chlamydial developmental cycle, i.e. after cell lysis (Rasmussen et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, after infection with serovar L2, a progressive increase in the level of IL-11 mRNA upregulation over the time of infection was detected, reaching a level of expression 12.7 times higher than that in uninfected cells (Table 1). As previous studies reported the detection by reverse transcriptase±polymerase chain reaction (RT±PCR) of IL-8 and IL-1a mRNA in HeLa cells infected with C. trachomatis serovar L2 (Rasmussen et al, 1997;, we expected to find an upregulation of these genes with the cDNA array method. However, no IL-8 mRNA was detected in polarized HeLa cells infected with either serovar for all times tested.…”

Section: Infection Of Hela Cells With C Trachomatis Induced a Pmn Chmentioning

confidence: 97%

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Chlamydial infection of polarized HeLa cells induces PMN chemotaxis but the cytokine profile varies between disseminating and non-disseminating strains

Dessus-Babus

Knight

Wyrick³

2000

Cell Microbiol

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Chlamydial heat shock proteins and disease pathology: New paradigms for old problems?

LaVerda

Kalayoglu

Byrne

1999

Infect. Dis. Obstet. Gynecol.

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The mucosal pathogen Chlamydia trachomatis affects hundreds of millions of people worldwide and is a significant cause of sexually transmitted disease. Although most acute infections can be easily managed, complications often occur that can be especially severe in women. It has been proposed that increased exposure to conserved chlamydial antigens, such as through reinfection or persistent infection, results in chronic inflammation and tissue scarring and contributes to the pathogenesis of endometrial and fallopian tube damage. This immunopathologic damage is believed to be a principal cause of ectopic pregnancy and tubal factor infertility. The chlamydial heat shock protein Hsp60, a homolog of Escherichia coli GroEL, has been identified as one protein capable of eliciting intense mononuclear inflammation. Furthermore, several studies have revealed a correlation between Hsp60 responses and the immunopathologic manifestations of human chlamydial disease. The role of additional antigens in the immunopathologic response to chlamydiae is currently undefined. A prime candidate, however, is the chlamydial GroES homolog Hsp10, which is genetically and physiologically linked to Hsp60. Recent studies provide data to suggest that immune reactivity to Hsp10 is significantly associated with tubal infertility in a chlamydiae-exposed population. Chlamydia pneumoniae is a more recently defined chlamydial species that has been implicated in a variety of ways with chronic disease processes, such as adult onset asthma and atherosclerosis. Evidence indicates that Hsp60 is present in human atheroma and may play a role in lesion development by direct activation of macrophages. Hsp60 causes the elaboration of inflammatory cytokines, the induction of metalloproteinase, and the oxidation of low density lipoprotein. Each of these events is directly associated with the progress of atherosclerosis. Thus, chlamydial heat shock proteins may function in at least two ways to promote chronic disease: first by direct antigenic stimulation and second as signal transducers that result in macrophage activation. These concepts in disease pathology are discussed in the context of chlamydial infections.

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Secretion of proinflammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis.

Cited by 468 publications

References 44 publications

Chlamydia trachomatis infection and persistence of human papillomavirus

Chlamydia trachomatis infection and persistence of human papillomavirus

Chlamydial infection of polarized HeLa cells induces PMN chemotaxis but the cytokine profile varies between disseminating and non-disseminating strains

Chlamydial heat shock proteins and disease pathology: New paradigms for old problems?

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