Microarray Analysis of a<i>Chlamydia pneumoniae</i>–Infected Human Epithelial Cell Line by Use of Gene Ontology Hierarchy

Alvesalo, Joni; Greco, Dario; Leinonen, Maija; Raitila, Tuomas; Vuorela, Pia; Auvinen, Petri

doi:10.1086/524142

Cited by 23 publications

(16 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…28,29 Local high Ca 2+ concentrations and Ca 2+ -binding protein accumulate in the proximity of chlamydial aggregates and they are pivotal for the proper formation of chlamydial inclusions. In a recent microarray study by Alvesalo et al, 30 expression levels of genes associated with regulation of Ca 2+ homeostasis were significantly changed by C. pneumoniae infection in HL cells. The results presented in the current work indicate that Ca 2+ modulators alone have only a minor effect on acute C. pneumoniae infection in HL cells, or in the case of verapamil, may even increase the number of chlamydial inclusions.…”

Section: Discussionmentioning

confidence: 93%

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

et al. 2011

Self Cite

View full text Add to dashboard Cite

Besides small molecules from medicinal chemistry, natural products are still major sources of innovative therapeutic agents for various conditions, including infectious diseases. Here we present the first attempt to design a combination treatment targeted against Chlamydia pneumoniae infection using coadministration of natural phenolics with calcium (Ca 2+ ) modulators, and also the concomitant administration of these compounds with doxycycline. An in vitro acute C. pneumoniae model in human lung epithelial cells was used and Loewe additivity model was applied to evaluate the effects. In general, the phenolic compounds, quercetin, luteolin, rhamnetin and octyl gallate did not improve the antichlamydial effect of doxycycline, and, in some cases, resulted in antagonistic effects. The combination of doxycycline and Ca 2+ modulators (isradipine, verapamil and thapsigargin) was at most additive, and at subinhibitory concentrations of doxycycline, often even antagonistic. The Ca 2+ modulators showed no inhibitory effects on C. pneumoniae growth alone, whereas the coadminstration of Ca 2+ modulators with phenolic compounds resulted in potentiation of the antichlamydial effect of phenolic compounds. Verapamil (100 lM) was synergistic with low quercetin and luteolin concentrations (0.39 and 1.56 lM), whereas 10 lM isradipine was synergistic with high quercetin, rhamnetin and octyl gallate concentrations (12.5 lM and 100 lM). Use of thapsigargin with the phenolic compounds resulted in the most intense synergism. Interaction indices 0.12 and 0.14 were achieved with 0.39 lM luteolin and 10 and 100 nM thapsigargin, respectively. To conclude, the observed results indicate that the Ca 2+ modulators potentiate the antichlamydial effects of the phenolic compounds.

show abstract

Section: Discussionmentioning

confidence: 93%

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…Since there are no suitable animal models for Chlamydia , all gene expression profiling studies reporting on host cell responses to chlamydial infections are performed with infected cell lines and tissues (e.g., Stephens, 2003; Alvesalo et al, 2008; Amirshahi et al, 2011). Not unexpectedly, these studies provide only little information on differentially expressed metabolic genes.…”

Section: Metabolic Host Responses To Selected Intracellular Bacterialmentioning

confidence: 99%

“…It will be interesting to find out whether these transporter proteins are incorporated into the host cell cytoplasmic membrane or recruited to the Chlamydia containing vacuole (“inclusion body”). Not surprisingly, none of these transporter genes upregulated in the tissue samples have been found differentially expressed in productively and persistently Chlamydia -infected HeLa or HL cells using transcriptomic (Eickhoff et al, 2007; Alvesalo et al, 2008) or proteomic approaches (Savijoki et al, 2008). As discussed above, nutrient uptake is already induced in these transformed cell lines.…”

Section: Metabolic Host Responses To Selected Intracellular Bacterialmentioning

confidence: 99%

Metabolic host responses to infection by intracellular bacterial pathogens

Eisenreich¹,

Heesemann²,

Rudel³

et al. 2013

Front. Cell. Infect. Microbiol.

171

152

View full text Add to dashboard Cite

The interaction of bacterial pathogens with mammalian hosts leads to a variety of physiological responses of the interacting partners aimed at an adaptation to the new situation. These responses include multiple metabolic changes in the affected host cells which are most obvious when the pathogen replicates within host cells as in case of intracellular bacterial pathogens. While the pathogen tries to deprive nutrients from the host cell, the host cell in return takes various metabolic countermeasures against the nutrient theft. During this conflicting interaction, the pathogen triggers metabolic host cell responses by means of common cell envelope components and specific virulence-associated factors. These host reactions generally promote replication of the pathogen. There is growing evidence that pathogen-specific factors may interfere in different ways with the complex regulatory network that controls the carbon and nitrogen metabolism of mammalian cells. The host cell defense answers include general metabolic reactions, like the generation of oxygen- and/or nitrogen-reactive species, and more specific measures aimed to prevent access to essential nutrients for the respective pathogen. Accurate results on metabolic host cell responses are often hampered by the use of cancer cell lines that already exhibit various de-regulated reactions in the primary carbon metabolism. Hence, there is an urgent need for cellular models that more closely reflect the in vivo infection conditions. The exact knowledge of the metabolic host cell responses may provide new interesting concepts for antibacterial therapies.

show abstract

Microarray Analysis of aChlamydia pneumoniae–Infected Human Epithelial Cell Line by Use of Gene Ontology Hierarchy

Cited by 23 publications

References 31 publications

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro

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

Metabolic host responses to infection by intracellular bacterial pathogens

Contact Info

Product

Resources

About