<i>Chlamydia trachomatis</i>Infection Alters Host Cell Transcription in Diverse Cellular Pathways

Xia, Minsheng; Bumgarner, Roger E.; Lampe, Mary F.; Stamm, Walter E.

doi:10.1086/367962

Cited by 71 publications

(53 citation statements)

References 33 publications

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“…We chose the Affymetrix HG-U133 Plus 2.0 Gene Chip for this study. This gene chip contains Ͼ47,000 genes and gene transcripts and allows for more comprehensive evaluation of the host gene response to Chlamydia infection compared with the gene chips used in previous studies (38,39). Consistent with observations from these studies, we found that Chlamydia infection induced genes of cell proliferation, transcription, biosynthesis and metabolism, signal transduction, inflammation, and host defense.…”

Section: Discussionsupporting

confidence: 88%

Up-Regulation of the JAK/STAT1 Signal Pathway during Chlamydia trachomatis Infection

Lad

Fukuda

et al. 2005

The Journal of Immunology

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Chlamydia trachomatis infection is the most common cause of sexually transmitted disease, leading to female pelvic inflammatory disease and infertility. The disease process has been linked to cellular response to this bacterial pathogen. This obligate intracellular pathogen infects macrophages, fibroblast cells, and epithelial and endothelial cells. We show in this study that infection of cervical epithelial cells, the primary target of Chlamydia trachomatis, leads to up-regulation and activation of the JAK/STAT signal pathway. Specifically, Chlamydia trachomatis infection of HeLa 229 cells selectively induces STAT1, STAT2, and IFN-stimulated transcription factor 3γ expression and promotes STAT1 activation. The up-regulation of STAT1 is dependent on bacterial replication, because treatment of infected cells with antibiotics prevents STAT1 up-regulation. By analysis of the gene transcriptional and cytokine expression profiles of host cells combined with the use of neutralizing Abs, we show that IFN-β production is critical for STAT1 induction in epithelial cells. Finally, we demonstrate that the host up-regulates STAT1 to restrict bacterial infection, because Chlamydia propagates more efficiently in STAT1-null or STAT1 knockdown cells, whereas Chlamydia growth is inhibited in cells with up-regulated STAT1 expression. This study demonstrates that the infected cells up-regulate the host innate antimicrobial response to chlamydial infection. It also highlights the importance of cellular response by nonimmune cells in host clearance of chlamydial infection.

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Section: Discussionsupporting

confidence: 88%

Up-Regulation of the JAK/STAT1 Signal Pathway during Chlamydia trachomatis Infection

Lad

Fukuda

et al. 2005

The Journal of Immunology

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“…Previous studies using DNA microarray techniques have shown that Chlamydia infection upregulates genes of cell proliferation, transcriptional regulation, and inflammation (16,45). To fully evaluate host responses of cervical epithelial cells to Chlamydia infection, we used the newly released Affymetrix Gene Chip Human Genome HG-U133 plus 2.0.…”

Section: Resultsmentioning

confidence: 99%

Activation of Lipid Metabolism Contributes to Interleukin-8 Production duringChlamydia trachomatisInfection of Cervical Epithelial Cells

et al. 2005

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Chlamydia trachomatis infection is the most common cause of bacterial sexually transmitted diseases. Infection of the urogenital tract by C. trachomatis causes chronic inflammation and related clinical complications. Unlike other invasive bacteria that induce a rapid cytokine/chemokine production, chlamydial infection induces delayed inflammatory response and proinflammatory chemokine production that is dependent on bacterial growth. We present data here to show that the lipid metabolism required for chlamydial growth contributes to Chlamydia-induced proinflammatory chemokine production. By gene microarray profiling, validated with biochemical studies, we found that C. trachomatis LGV2 selectively upregulated PTGS2 (COX2) and PTGER4 (EP4) in cervical epithelial HeLa 229 cells. COX2 is an enzyme that catalyzes the rate-limiting step of arachidonic acid conversion to prostaglandins, including prostaglandin E2 (PGE2) and other eicosanoids, whereas EP4 is a subtype of cell surface receptors for PGE2. We show that Chlamydia infection induced COX2 protein expression in both epithelial cells and peripheral blood mononuclear cells and promoted PGE2 release. Exogenous PGE2 was able to induce interleukin-8 release in HeLa 229 epithelial cells. Finally, we demonstrated that interleukin-8 induction by Chlamydia infection or PGE2 treatment was dependent on extracellular signal-regulated kinase/mitogen-activated protein activity. Together, these data demonstrate that the host lipid remodeling process required for chlamydial growth contributes to proinflammatory chemokine production. This study also highlights the importance of maintaining a balanced habitat for parasitic pathogens as obligate intracellular organisms.

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“…Many times, this manifests itself in alterations to the transcriptome, which have been observed for a variety of Chlamydia species (57)(58)(59). However, a recent report demonstrated that C. trachomatis infection can alter the abundance of host proteins without altering levels of transcripts (60).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

et al. 2016

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The direct major histocompatibility complex (MHC) class I antigen presentation pathway ensures intracellular peptides are displayed at the cellular surface for recognition of infected or transformed cells by CD8 ؉ cytotoxic T lymphocytes. Chlamydia spp. are obligate intracellular bacteria and, as such, should be targeted by CD8 ؉ T cells. It is likely that Chlamydia spp. have evolved mechanisms to avoid the CD8 ؉ killer T cell responses by interfering with MHC class I antigen presentation. Using a model system of self-peptide presentation which allows for posttranslational control of the model protein's stability, we tested the ability of various Chlamydia species to alter direct MHC class I antigen presentation. Infection of the JY lymphoblastoid cell line limited the accumulation of a model host protein and increased presentation of the model-protein-derived peptides. Enhanced selfpeptide presentation was detected only when presentation was restricted to defective ribosomal products, or DRiPs, and total MHC class I levels remained unaltered. Skewed antigen presentation was dependent on a bacterial synthesized component, as evidenced by reversal of the observed phenotype upon preventing bacterial transcription, translation, and the inhibition of bacterial lipooligosaccharide synthesis. These data suggest that Chlamydia spp. have evolved to alter the host antigen presentation machinery to favor presentation of defective and rapidly degraded forms of self-antigen, possibly as a mechanism to diminish the presentation of peptides derived from bacterial proteins.

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Chlamydia trachomatisInfection Alters Host Cell Transcription in Diverse Cellular Pathways

Cited by 71 publications

References 33 publications

Up-Regulation of the JAK/STAT1 Signal Pathway during Chlamydia trachomatis Infection

Up-Regulation of the JAK/STAT1 Signal Pathway during Chlamydia trachomatis Infection

Activation of Lipid Metabolism Contributes to Interleukin-8 Production duringChlamydia trachomatisInfection of Cervical Epithelial Cells

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

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