Determination of chlamydial load and immune parameters in asymptomatic, symptomatic and infertile women

Agrawal, Tanvi; Vats, Vikas; Salhan, Sudha; Mittal, Aliza

doi:10.1111/j.1574-695x.2008.00530.x

Cited by 21 publications

(17 citation statements)

References 27 publications

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“…Chlamydial infection of estradiol-treated mice may more closely mimic asymptomatic chlamydial infection in women, however (24). In support of this possibility, Agrawal et al observed lower levels of several cytokines and chemokines in cervical washes from C. trachomatis-infected asymptomatic women compared to women who were symptomatic for infection (2).…”

Section: Discussionsupporting

confidence: 49%

Chlamydial Infection Increases Gonococcal Colonization in a Novel Murine Coinfection Model

et al. 2011

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Genital tract infections caused by Neisseria gonorrhoeae and Chlamydia trachomatis serovars D to K occur at high incidence in many areas of the world. Despite high rates of coinfection with these pathogens, investigations of host-parasite interactions have focused on each pathogen individually. We describe here a coinfection model in which female BALB/c mice were first infected with the mouse Chlamydia species C. muridarum and then inoculated with N. gonorrhoeae following treatment with water-soluble 17␤-estradiol to promote long-term gonococcal infection. Viable gonococci and chlamydiae were recovered for an average of 8 to 10 days, and diplococci and chlamydial inclusions were observed in lower genital tract tissue by immunohistochemical staining. Estradiol treatment reduced proinflammatory cytokine and chemokine levels in chlamydia-infected mice; however, coinfected mice had a higher percentage of vaginal neutrophils compared to mice infected with either pathogen alone. We detected no difference in pathogen-specific antibody levels due to coinfection. Interestingly, significantly more gonococci were recovered from coinfected mice compared to mice infected with N. gonorrhoeae alone. We found no evidence that C. muridarum increases gonococcal adherence to, or invasion of, immortalized murine epithelial cells. However, increased vaginal concentrations of inflammatory mediators macrophage inflammatory protein 2 and tumor necrosis factor alpha were detected in C. muridarum-infected mice prior to inoculation with N. gonorrhoeae concurrently with the downregulation of cathelicidin-related antimicrobial peptide and secretory leukocyte peptidase inhibitor genes. We conclude that female mice can be successfully infected with both C. muridarum and N. gonorrhoeae and that chlamydia-induced alterations in host innate responses may enhance gonococcal infection.Chlamydia and gonorrhea are the two most common notifiable infectious diseases in the United States, with over 1 million cases of chlamydia and 350,000 cases of gonorrhea reported to the Centers for Disease Control in 2008 (9). Actual rates of infection are much higher due to high rates of asymptomatic infection (50). As many as 50 to 70% of individuals with gonorrhea also have a chlamydial infection (20,50,55), and empirical treatment for chlamydia upon detection of N. gonorrhoeae is recommended (10,27). Neisseria gonorrhoeae and Chlamydia trachomatis are both Gram-negative, humanspecific pathogens. In symptomatic infections, both organisms elicit a proinflammatory response characterized by the influx of polymorphonuclear leukocytes (PMNs). Clinically, gonorrhea is typically more pyogenic. Postinfection complications can occur with either pathogen and complications are generally more common and more severe in women. Infections that ascend to the upper genital tract in women lead to pelvic inflammatory disease (PID), the complications of which include chronic pelvic pain, ectopic pregnancy, and infertility (28, 78).The incidence (50, 55), transmission (45,46,48), and...

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Section: Discussionsupporting

confidence: 49%

Chlamydial Infection Increases Gonococcal Colonization in a Novel Murine Coinfection Model

et al. 2011

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“…To our knowledge, only two studies have examined the influence of STIs on hsCRP or CRP . The first of these studies observed higher levels of CRP in pregnant women with Trichomonas vaginalis infection than in those without infection, and the second observed higher levels in C trachomatis positive women with mucopurulent cervicitis (ie, symptomatic infection) or infertility than in asymptomatic, C trachomatis positive women . While these findings are difficult to compare directly to our results because we do not have information on symptoms, we believe our results are consistent with these findings based on the typical presentation of chlamydia and gonorrhea in men.…”

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Insight into infection‐mediated prostate damage: Contrasting patterns of C‐reactive protein and prostate‐specific antigen levels during infection

et al. 2017

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Background To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male U.S. military members and compared our findings to those for PSA. Methods We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220–256 controls. Results Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (p<0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p=0.038–0.077). Conclusions These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (e.g., prostate infection) and indirect (e.g., systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk.

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“…Some data suggest that CD8 + T cells play some role at least in the initial phase of infection resolution, whereas in mice, they are dispensable. Both CD4 + and CD8 + cells are recruited to the endocervix during C. trachomatis infection in humans, and the proportion appears to be situational, based on clinical presentation [80]. In this study, higher organism load in cervical swab samples from women with chlamydial infection was associated with an increased number of local CD4 + cells [80].…”

Section: Usefulness Of Animal Models In Studying Human C Trachomatismentioning

confidence: 86%

“…Both CD4 + and CD8 + cells are recruited to the endocervix during C. trachomatis infection in humans, and the proportion appears to be situational, based on clinical presentation [80]. In this study, higher organism load in cervical swab samples from women with chlamydial infection was associated with an increased number of local CD4 + cells [80]. Because of the cross-sectional nature of the study, it is unclear whether this represents recruitment of protective cells in response to increasing chlamydial load or a relative ineffectiveness of CD4 + T cells in human infection.…”

Section: Usefulness Of Animal Models In Studying Human C Trachomatismentioning

confidence: 95%

Duration of Untreated Chlamydial Genital Infection and Factors Associated with Clearance: Review of Animal Studies

2010

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Chlamydia trachomatis is an important cause of sexually transmitted infection that can manifest as acute cervicitis, pelvic inflammatory disease, and most commonly, chronic asymptomatic infection. The basis of this wide spectrum of manifestations and the factors that lead to clearance or chronic infection are poorly understood. We reviewed specific literature pertaining to clearance of primary genital tract infections in animal models, including mice, guinea pigs, pigs, sheep, and nonhuman primates. T helper 1 cell responses involved in cell-mediated immunity are key immune parameters that define efficient clearance in the murine and guinea pig models of chlamydial infection, which are useful for studying C. trachomatis clearance. However, there may be some differences between humans and other animals in innate and adaptive immune responses to chlamydial infection. Studies have suggested that differences in the induced T cell subsets and the species-specific differences in interferon gamma-mediated effector mechanisms may play a significant role in these discrepancies. To close these gaps in knowledge, translational research in humans is a critical next step. However, for questions about specific mechanisms of host-pathogen interaction that cannot be answered feasibly or ethically in humans, animal models will continue to be important. Future research should include use of humanized and nonmurine models that establish prolonged infection to improve understanding of chronic human infections.

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Determination of chlamydial load and immune parameters in asymptomatic, symptomatic and infertile women

Cited by 21 publications

References 27 publications

Chlamydial Infection Increases Gonococcal Colonization in a Novel Murine Coinfection Model

Chlamydial Infection Increases Gonococcal Colonization in a Novel Murine Coinfection Model

Insight into infection‐mediated prostate damage: Contrasting patterns of C‐reactive protein and prostate‐specific antigen levels during infection

Duration of Untreated Chlamydial Genital Infection and Factors Associated with Clearance: Review of Animal Studies

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