Chlamydia trachomatis-Infected Epithelial Cells and Fibroblasts Retain the Ability To Express Surface-Presented Major Histocompatibility Complex Class I Molecules

Kägebein, Danny; Gutjahr, Melanie; Grosse, C.; Vogel, Annette B.; Rödel, Jürgen; Knittler, Michael R.

doi:10.1128/iai.01473-13

Cited by 10 publications

(8 citation statements)

References 62 publications

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“…Similar to several herpesviruses, modest decreases in total MHC class I expression have been reported in cells infected with a variety of Chlamydia species (7-9), but this does not always occur (61), consistent with our reported data (see Fig. 3F).…”

Section: Discussionsupporting

confidence: 82%

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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Section: Discussionsupporting

confidence: 82%

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

et al. 2016

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“…The susceptibility and growth permissiveness of different cell lines to infection by C. trachomatis enables examination of the host-pathogen relationship [42][43][44][45]. Such studies frequently find differences between strains in their ability to enter the host cell, and complete their developmental cycle [46].…”

Section: Discussionmentioning

confidence: 99%

Chlamydial clinical isolates show subtle differences in persistence phenotypes and growth in vitro

Thomas

Lawrence

Kroon

et al. 2021

Access Microbiology

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Urogenital Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection throughout the world. While progress has been made to better understand how type strains develop and respond to environmental stress in vitro, very few studies have examined how clinical isolates behave under similar conditions. Here, we examined the development and persistence phenotypes of several clinical isolates, to determine how similar they are to each other, and the type strain C. trachomatis D/UW-3/Cx. The type strain was shown to produce infectious progeny at a higher magnitude than each of the clinical isolates, in each of the six tested cell lines. All chlamydial strains produced the highest number of infectious progeny at 44 h post-infection in the McCoy B murine fibroblast cell line, yet showed higher levels of infectivity in the MCF-7 human epithelial cell line. The clinical isolates were shown to be more susceptible than the type strain to the effects of penicillin and iron deprivation persistence models in the MCF-7 cell line. While subtle differences between clinical isolates were observed throughout the experiments conducted, no significant differences were identified. This study reinforces the importance of examining clinical isolates when trying to relate in vitro data to clinical outcomes, as well as the importance of considering the adaptations many type strains have to being cultured in vitro.

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“…Kägebein et al [68] then demonstrated that Ct infection does not lead to alteration in normal MHC Class-I expression, maturation or surface presentation. This implies that Ct infected cells are unlikely to be targets for missing-self reactions mediated by NK cells which selectively monitor down-regulation or loss of self-type MHC class I on target cells.…”

Section: Discussionmentioning

confidence: 99%

“…The chlamydial protease, CPAF has been reported to interfere with the surface presentation of HLA class I molecules [14] , [64] – [66] , but recently this has been called in to question by Chen et al [67] . Kägebein et al [68] then demonstrated that Ct infection does not lead to alteration in normal MHC Class-I expression, maturation or surface presentation. This implies that Ct infected cells are unlikely to be targets for missing-self reactions mediated by NK cells which selectively monitor down-regulation or loss of self-type MHC class I on target cells.…”

Section: Discussionmentioning

confidence: 99%

Conjunctival Scarring in Trachoma Is Associated with the HLA-C Ligand of KIR and Is Exacerbated by Heterozygosity at KIR2DL2/KIR2DL3

et al. 2014

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Background Chlamydia trachomatis is globally the predominant infectious cause of blindness and one of the most common bacterial causes of sexually transmitted infection. Infections of the conjunctiva cause the blinding disease trachoma, an immuno-pathological disease that is characterised by chronic conjunctival inflammation and fibrosis. The polymorphic Killer-cell Immunoglobulin-like Receptors (KIR) are found on Natural Killer cells and have co-evolved with the Human Leucocyte Antigen (HLA) class I system. Certain genetic constellations of KIR and HLA class I polymorphisms are associated with a number of diseases in which modulation of the innate responses to viral and intracellular bacterial pathogens is central.MethodologyA sample of 134 Gambian pedigrees selected to contain at least one individual with conjunctival scarring in the F1 generation was used. Individuals (n = 830) were genotyped for HLA class I and KIR gene families. Family Based Association Tests and Case Pseudo-control tests were used to extend tests for transmission disequilibrium to take full advantage of the family design, genetic model and phenotype.Principle findingsWe found that the odds of trachomatous scarring increased with the number of genome copies of HLA-C2 (C1/C2 OR = 2.29 BHP-value = 0.006; C2/C2 OR = 3.97 BHP-value = 0.0004) and further increased when both KIR2DL2 and KIR2DL3 (C2/C2 OR = 5.95 BHP-value = 0.006) were present.ConclusionsTo explain the observations in the context of chlamydial infection and trachoma we propose a two-stage model of response and disease that balances the cytolytic response of KIR expressing NK cells with the ability to secrete interferon gamma, a combination that may cause pathology. The data presented indicate that HLA-C genotypes are important determinants of conjunctival scarring in trachoma and that KIR2DL2/KIR2DL3 heterozygosity further increases risk of conjunctival scarring in individuals carrying HLA-C2.

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Chlamydia trachomatis-Infected Epithelial Cells and Fibroblasts Retain the Ability To Express Surface-Presented Major Histocompatibility Complex Class I Molecules

Cited by 10 publications

References 62 publications

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

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

Chlamydial clinical isolates show subtle differences in persistence phenotypes and growth in vitro

Conjunctival Scarring in Trachoma Is Associated with the HLA-C Ligand of KIR and Is Exacerbated by Heterozygosity at KIR2DL2/KIR2DL3

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