Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women

Zheng, Xiaojing; O’Connell, Catherine M.; Zhong, Wujuan; Poston, Taylor B.; Wiesenfeld, Harold C.; Hillier, Sharon L.; Trent, Maria; Gaydos, Charlotte A.; Tseng, George C.; Taylor, Brandie D.; Darville, Toni

doi:10.3389/fcimb.2018.00307

Cited by 18 publications

(12 citation statements)

References 33 publications

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“…The cytokine ratios determined to be associated with chlamydial susceptibility can be prospectively examined in an independent cohort to test their ability to predict endometrial infection. Incorporation of host gene expression signatures [19,49], and other potential factors associated with chlamydial susceptibility such as the vaginal microbiome [50] could improve the predictive accuracy and may also allow for prediction of risk for repeat infection. In addition, our determination of protective responses that are detectable at the cervical mucosa during natural infection have provided important information for vaccine development, regarding specific chemokines and cytokines that might be incorporated as adjuvants to drive Th1 responses necessary for protection against this highly prevalent intracellular pathogen.…”

Section: Discussionmentioning

confidence: 99%

Cervical Cytokines Associated With Chlamydia trachomatis Susceptibility and Protection

Poston

Lee

Darville

et al. 2019

The Journal of Infectious Diseases

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Background. Chlamydia trachomatis can cause reproductive morbidities after ascending to the upper genital tract of women, and repeated infection can lead to worse disease. Data related to protective immune responses at the cervical mucosa that could limit chlamydial infection to the cervix and/or prevent reinfection inform vaccine approaches and biomarkers of risk. Methods. We measured 48 cytokines in cervical secretions from women having chlamydial cervical infection alone (n = 92) or both cervical and endometrial infection (n = 68). Univariable regression identified cytokines associated with differential odds of endometrial infection and reinfection risk, and multivariable stepwise regression identified cytokine ratios associated with differential risk. Results. Elevated interleukin (IL) 15/CXCL10 (odds ratio [OR], 0.55 [95% confidence interval {CI}, .37-.78]), IL-16/tumor necrosis factor-α (OR, 0.66 [95% CI, .45-.93]), and CXCL14/IL-17A (OR, 0.73 [95% CI, .54-.97]) cytokine ratios were significantly (P ≤ .05) associated with decreased odds of endometrial infection. A higher Flt-3L/IL-14 ratio was significantly (P = .001) associated with a decreased risk of reinfection (hazard ratio, 0.71 [95% CI, .58-.88]). Conclusions. Cytokines involved in humoral, type I interferon, and T-helper (Th) 17 responses were associated with susceptibility to C. trachomatis, whereas cytokines involved in Th1 polarization, recruitment, and activation were associated with protection against ascension and reinfection.

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Section: Discussionmentioning

confidence: 99%

Cervical Cytokines Associated With Chlamydia trachomatis Susceptibility and Protection

Poston

Lee

Darville

et al. 2019

The Journal of Infectious Diseases

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“…Transcriptional profiling of trachoma conjunctival samples showed transcriptional networks connected to the innate immune response (42,43). Biomarker studies of women with chlamydial endometritis found increased expression levels of myeloid mediators of inflammation (44). We found that Pgp3-mediated persistent infection caused chronic macrophage immunopathology in the mouse model.…”

Section: Discussionmentioning

confidence: 72%

Chlamydia trachomatis Plasmid Gene Protein 3 Is Essential for the Establishment of Persistent Infection and Associated Immunopathology

Yang

Kari

Lei

et al. 2020

mBio

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Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease afflicting hundreds of millions of people globally. A fundamental but poorly understood pathophysiological characteristic of chlamydial infection is the propensity to cause persistent infection that drives damaging inflammatory disease. The chlamydial plasmid is a virulence factor, but its role in the pathogenesis of persistent infection capable of driving immunopathology is unknown. Here, we show by using mouse and nonhuman primate infection models that the secreted plasmid gene protein 3 (Pgp3) is essential for establishing persistent infection. Ppg3-dependent persistent genital tract infection resulted in a severe endometritis caused by an intense infiltration of endometrial submucosal macrophages. Pgp3 released from the cytosol of lysed infected oviduct epithelial cells, not organism outer membrane-associated Pgp3, inhibited the chlamydial killing activity of antimicrobial peptides. Genetic Pgp3 rescue experiments in cathelin-related antimicrobial peptide (CRAMP)-deficient mice showed Pgp3-targeted antimicrobial peptides to subvert innate immunity as a pathogenic strategy to establish persistent infection. These findings provide important advances in understanding the role of Pgp3 in the pathogenesis of persistent chlamydial infection and associated immunopathology. IMPORTANCE Chlamydia trachomatis can cause persistent infection that drives damaging inflammatory responses resulting in infertility and blindness. Little is known about chlamydial genes that cause persistence or factors that drive damaging pathology. In this work, we show that the C. trachomatis plasmid protein gene 3 (Pgp3) is the essential virulence factor for establishing persistent female genital tract infection and provide supportive evidence that Pgp3 functions similarly in a nonhuman primate trachoma model. We further show that persistent Ppg3-dependent infection drives damaging immunopathology. These results are important advances in understanding the pathophysiology of chlamydial persistence.

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“…The expression of LYSMD2 was also downregulated in IF birds compared to both AL and CR. Although the actual function of the gene is yet unknown, it appears to be related to myeloid cell-mediated inflammation in humans (37) and has been found to be overexpressed in mice with fatty liver-induced hepatocellular carcinomas (38). In dogs undergoing surgery for congenital portosystemic shunts, low hepatic expression of NFE2L2 during surgery is a predictor of poor recovery (39).…”

Section: Discussionmentioning

confidence: 99%

Intermittent fasting induces chronic changes in the hepatic gene expression of Red Junglefowl (Gallus gallus)

Lindholm

Batakis

Altimiras

et al. 2019

Preprint

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Background: Intermittent fasting, the implementation of fasting periods of at least 12 consecutive hours on a daily to weekly basis, has received a lot of attention in recent years for imparting the life-prolonging and health-promoting effects of caloric restriction with no or only moderate actual restriction of caloric intake. Intermittent fasting is also widely practiced in the rearing of so-called broiler breeders, the parent stock of meat-type chickens, who require strict feed restriction regimens to prevent the serious health problems associated with their voracious appetites. Although intermittent fasting has been extensively used in this context to reduce feed competition and its resulting stress it has not usually been considered as a health-span promoter, but presents an alternative and complementary model to rodent studies. In both mammals and birds, the liver is one of the main responders to variations in energy balance. In this paper we examine the liver transcriptomics of wild-type Red Junglefowl chickens fed either ad libitum, chronically restricted to around 70% of ad libitum daily or intermittently fasted on a 2:1 (2 days fed, 1 day fasted) schedule without actual caloric restriction using a microarray. Results: We find large effects of feeding regimen on liver transcriptomics, with most of the affected genes relating to energy metabolism. Interestingly we also find large, chronic effects on the transcription of a battery of cell proliferation-promoting genes. Similar regenerative effects have been reported in rodents, where they have been associated with reduced levels of circulating leptin. A small number of inflammation-related genes also show chronically changed expression profiles. Conclusions: The increase in proliferative potential suggested by the gene expression changes reported here is a first indication that birds and mammals respond similarly to intermittent fasting practices. Our findings may indicate that the health benefits of periodic caloric restriction are ubiquitous and note restricted to mammals alone. The mechanisms underpinning these benefits are, however, unclear as leptin has been associated with these benefits in mammals but does not have endocrine function in birds. The observed effects on inflammation-related genes may be either beneficial or detrimental for the animal and could warrant further investigation.

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Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women

Cited by 18 publications

References 33 publications

Cervical Cytokines Associated With Chlamydia trachomatis Susceptibility and Protection

Cervical Cytokines Associated With Chlamydia trachomatis Susceptibility and Protection

Chlamydia trachomatis Plasmid Gene Protein 3 Is Essential for the Establishment of Persistent Infection and Associated Immunopathology

Intermittent fasting induces chronic changes in the hepatic gene expression of Red Junglefowl (Gallus gallus)

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