Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human blood leukocytes to discriminate patients with acute infections

ABSTRACT: Each infectious agent represents a unique combination of pathogen-associated molecular patterns that interact with specific pattern-recognition receptors expressed on immune cells. Therefore, we surmised that the blood immune cells of individuals with different infections might bear discriminative transcriptional signatures. Gene expression profiles were obtained for 131 peripheral blood samples from pediatric patients with acute infections caused by influenza A virus, Gram-negative (Escherichia coli) or Gram-positive (Staphylococcus aureus and Streptococcus pneumoniae) bacteria. Thirty-five genes were identified that best discriminate patients with influenza A virus infection from patients with either E coli or S pneumoniae infection. These genes classified with 95% accuracy (35 of 37 samples) an independent set of patients with either influenza A, E coli, or S pneumoniae infection. A different signature discriminated patients with E coli versus S aureus infections with 85% accuracy (34 of 40). Furthermore, distinctive gene expression patterns were observed in patients presenting with respiratory infections of different etiologies. Thus, microarray analyses of patient peripheral blood leukocytes might assist in the differential diagnosis of infectious diseases. Experiment Overall Design: Entire study included 144 samples. Only 143 are included in this series because the CHP/CEL file was not available for sample PBMC_Healthy_INF295.

ORGANISM(S): Homo sapiens

SUBMITTER: Damien Chaussabel

PROVIDER: E-GEOD-6269 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression patterns in blood leukocytes discriminate patients with acute infections.

Ramilo Octavio O Allman Windy W Chung Wendy W Mejias Asuncion A Ardura Monica M Glaser Casey C Wittkowski Knut M KM Piqueras Bernard B Banchereau Jacques J Palucka A Karolina AK Chaussabel Damien D

Blood 20061114 5

Each infectious agent represents a unique combination of pathogen-associated molecular patterns that interact with specific pattern-recognition receptors expressed on immune cells. Therefore, we surmised that the blood immune cells of individuals with different infections might bear discriminative transcriptional signatures. Gene expression profiles were obtained for 131 peripheral blood samples from pediatric patients with acute infections caused by influenza A virus, Gram-negative (Escherichia ...[more]

PMID: 17105821

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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. Keywords: pathogen comparison, time course

Project description:We profiled the expression of circulating microRNAs (miRNAs) in mice exposed to gram-positive and gram-negative bacteria using Illumina small RNA deep sequencing. Recombinant-specific gram-negative pathogen Escherichia coli (Xen14) and gram-positive pathogen Staphylococcus aureus (Xen29) were used to induce bacterial infection in mice at a concentration of 1 × 108 bacteria/100 μL of phosphate buffered saline (PBS). Small RNA libraries generated from the serum of mice after exposure to PBS, Xen14, Xen29, and Xen14+Xen29 via the routes of subcutaneous injection (I), cut wound (C), or under grafted skin (S) were analyzed using an Illumina HiSeq2000 Sequencer. Following exposure to gram-negative bacteria alone, no differentially expressed miRNA was found in the injection, cut, or skin graft models. Exposure to mixed bacteria induced a similar expression pattern of the circulating miRNAs to that induced by gram-positive bacterial infection. Upon gram-positive bacterial infection, 9 miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p, mir-215-5p) showed upregulation greater than 4-fold with a p-value < 0.01. Among them, mir-193b-3p, mir-133a-1-3p, and mir-133a-2-3p presented the most common miRNA targets expressed in the mice exposed to gram-positive bacterial infection. Male C57BL/6 mice (age, 10–12 weeks; weight, 30–35 g) were purchased from BioLasco (Yi-Lan, Taiwan). The mice were anesthetized by intraperitoneal injection of an anesthetic cocktail consisting of 0.1 mg/g ketamine and 0.01 mg/g xylazine. The anesthetized mice were restrained in a supine position on a heated pad to maintain body temperature at 37°C. Recombinant-specific gram-negative pathogen Escherichia coli (Xen14) and gram-positive pathogen Staphylococcus aureus (Xen29) purchased from Caliper (Caliper, USA) were used to induce bacterial infection in the mice at a concentration of 1 × 108 bacteria/100 μL of phosphate buffered saline (PBS). To create mixed gram-negative and gram-positive bacterial infection, 1 × 108 Xen14 bacteria and 1 × 108 Xen29 bacteria/100 μL of PBS were used for wound contamination. Three animal models were used to create bacterial infection routes: subcutaneous injection (hereafter referred to as (I)), cut wound (hereafter referred to as (C)), and skin grafting (hereafter referred to as (S)). In the (I) model, E. coli and/or S. aureus suspensions were injected subcutaneously into the backs of the mice using an Fr. 25 needle. In the (C) model, a 1 cm incision wound was created in the midline of the back, smeared with E. coli and/or S. aureus suspension, and the wound was closed directly with a 4-0 nylon suture. In the (S) model, a 1×1 cm rectangular full- thickness skin graft was lifted from the backs of the mice, E. coli and/or S. aureus suspensions were spread over the wound bed, and the skin graft was reattached and closed with a 4-0 nylon suture. An additional group of animals in each of these three models was inoculated with PBS to serve as a negative control. Small RNA libraries generated from the serum of mice after exposure to PBS, Xen14, Xen29, and Xen14+Xen29 via the routes of subcutaneous injection (I), cut wound (C), or under grafted skin (S) were analyzed using an Illumina HiSeq2000 Sequencer.

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Transcription profiling of human blood leukocytes to discriminate patients with acute infections

Publications

Gene expression patterns in blood leukocytes discriminate patients with acute infections.

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