Unknown,Transcriptomics,Genomics,Proteomics

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Sugar turns benefit of cholesterol into immune evasion in Helicobacter pylori infected C57BL/6 mice

ABSTRACT: Following the initial demonstration of Helicobacter pyloriâ??s pathogenic potential, evidence has been accumulated that H. pylori is the leading cause of gastric ulcers, carcinoma and lymphoma3. Cholesterol is a physiological constituent of membranes critical for their biophysical properties, but is stigmatised as mediating detrimental effects in obesity and cardiovascular disease. Since H. pylori is auxotrophic for cholesterol, we explored the assimilation of cholesterol by H. pylori upon infection. Here we show that H. pylori follows a cholesterol gradient and extracts the lipid from plasma membranes of epithelial cells for subsequent glycosylation. Cholesterol promotes phagocytosis of H. pylori by antigen-presenting cells such as macrophages and dendritic cells and enhances antigen-specific T cell responses. Consistently, cholesterol-rich diet during bacterial challenge leads to a reduction of the H. pylori burden in the stomach. Intrinsic a-glycosylation of cholesterol abrogates phagocytosis of H. pylori and subsequent T cell activation. Hence, we propose a novel mechanism regulating host-pathogen interaction which describes glycosylation of a lipid tipping the scales towards immune evasion or response. color-swap dye-reversal hybridizations

ORGANISM(S): Mus musculus

SUBMITTER: Christian Wunder

PROVIDER: E-GEOD-3878 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Cholesterol glucosylation promotes immune evasion by Helicobacter pylori.

Wunder Christian C Churin Yuri Y Winau Florian F Warnecke Dirk D Vieth Michael M Lindner Buko B Zähringer Ulrich U Mollenkopf Hans-Joachim HJ Heinz Ernst E Meyer Thomas F TF

Nature medicine 20060903 9

Helicobacter pylori infection causes gastric pathology such as ulcer and carcinoma. Because H. pylori is auxotrophic for cholesterol, we have explored the assimilation of cholesterol by H. pylori in infection. Here we show that H. pylori follows a cholesterol gradient and extracts the lipid from plasma membranes of epithelial cells for subsequent glucosylation. Excessive cholesterol promotes phagocytosis of H. pylori by antigen-presenting cells, such as macrophages and dendritic cells, and enhan ...[more]

PMID: 16951684

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Project description:Peumonia is the most common cause of death due to infectious diseases in the western hemisphere. The molecular events associated with pulmonary infections caused by Streptococcus pneumoniae and Influenza A virus are incompletely understood. Pathophysiological and protective processes are initiated by immune receptors specifically recognizing pathogenic structures serving to elicit a qualitatively and quantitatively adequate immune response. To provide a molecular framework towards a better understanding of the processes relevant in severe infectious pneumonia we performed a transcriptome analysis of lungs from mice infected with S. pneumoniae or Influenza A virus. Overall, we detected 1300 genes that exhibit significant differential expression after infection with either pathogen. Of those were approximately 36 % specific for pneumococcal and 30 % specific for the viral infection, yielding pathogen-specific as well as common inflammatory transcriptional signatures. Characteristically, these results resolve not only a differential response on the cytokine and chemokine level, although common induction of type I and type II interferons, TNFa, and IL-6 underlies both infections, but emphasize the potentially important role exerted by many genes implicated in the regulation and fine tuning of the inflammatory response. Furthermore, we noted a specific decrease in B cells after S. pneumoniae infection, which is not solely confined to the lung. Massive induction of apoptosis in pulmonary B cells could reflect a pneumococcal virulence strategy aiming against the lymphocyte population that is of utmost importance for the defence against capsulated bacteria. The pathophysiological consequences of Influenza A virus infection become obvious through differential induction of genes implicated in tissue regeneration and proliferation associated with detection of the emerging protective T cell response. These results may provide new insights into the pathogenesis and protective mechanisms important for the development of improved diagnostic and therapeutic strategies. Microarray analyses were performed as two-colour hybridizations. RNA was labelled with a Fluorescent Linear Amplification Kit (Agilent Technologies). Briefly, 4 Âµg total RNA was reverse transcribed with an oligo-dT-T7 promoter primer and MMLV-RT. Second strand synthesis was carried out with random hexamers. Fluorescent antisense cRNA was synthesized with either cyanine 3-CTP (Cy3-CTP) or cyanine 5-CTP (Cy5-CTP) and T7 polymerase. Purified products were quantified at A552nm for Cy3-CTP and A650nm for Cy5-CTP. Prior hybridization, 1.25 Âµg labelled cRNA each were fragmented, mixed with control targets and hybridization buffer according to the supplier's protocol (Agilent Technologies). Hybridizations were performed for 17 h at 60Â°C. The slides were washed according to the manufacturer's protocol and scanning of the arrays was performed with 5 Âµm resolution using a DNA microarray laser scanner (Agilent Technologies). To compensate for dye specific effects, and to ensure validity of the data, a colour swap analysis (fluorescence reversal) was performed. Features were extracted with the image analysis tool Version A6.1.1.1 from Agilent Technologies. Subsequent data analyses were carried out on the Rosetta Inpharmatics platform Resolver Built 3.2.2. Differential expression patterns were identified by applying 2-fold expression level cut-offs and an anti-correlation of the dye reversal experiments with an error weighted p-value < 0.05.

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Dataset Information

Sugar turns benefit of cholesterol into immune evasion in Helicobacter pylori infected C57BL/6 mice

Publications

Cholesterol glucosylation promotes immune evasion by Helicobacter pylori.

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