Unknown,Transcriptomics,Genomics,Proteomics

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Differentially expressed genes in human macrophages infected with clinical isolates of Mycobacterium avium displaying phenotypically and genotypically distinct characteristics

ABSTRACT: Mycobacterium avium is a significant opportunistic intracellular pathogen in humans, pigs and birds. Human and porcine infection with M. avium is mainly due to M. avium subsp. hominissuis, whereas birds are typically infected with M. avium subsp. avium. Reasons for this distribution of subspecies between the hosts are uncertain, but they might be due to differences in exposure or to different abilities to infect the respective hosts. We wanted to assay how isolates of the two subspecies interact with a human host in a macrophage model to gain more knowledge on possible differences in virulence. This study compares clinical isolates of M. avium with regards to their ability to invade and replicate intracellularly in human monocytes/macrophages and to the gene expression triggered in these cells upon infection. Further focus in the description of protocols is limited to the parts of the study that regards the expression analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Flatberg Arnar

PROVIDER: E-MTAB-1101 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Mycobacterium avium subspecies paratuberculosis (MAP) infection is established following the ingestion of bacteria, their penetration of the intestinal mucosa and subsequent events of the host-parasite interaction. These bacteria invade M cells, macrophages and are capable of resisting host defenses and multiply to reach very high numbers intracellular. Mycobactrium avium subsp. avium (MAA) is an antigenically and genetically similar organisms but is relatively nonpathogenic for cattle. MAA organisms appear to infect cattle, but unlike cattle infected with MAP, cattle infected with MAA typically mount an effective systemic immune response, form caseous granuloma, and eliminate the infection. This study was designed to understand the similarities and differences in the host responses during MAP and MAA infection. Neonatal calves were infected (ligated ileal loops) with PBS, MAP, or avirulent MAA following which samples were collected at 30 min, 1h, 2h, 4h, 8h, or 12h. Post-infection, RNA was collected, processed, and then hybridized to custom bovine gene expression arrays, each of which represented 13,258 transcripts spotted in duplicate. Arrays were normalized by scaling against the average reference intensity value (i.e., average across all arrays), normalized by global mean, and then log transformed before statistical analyses were performed. Pairwise comparisons of averaged signal values and StudentM-bM-^@M-^Ys t test were performed using GeneSifter software (VizX Labs, Seattle, WA). A fold-change of at least 1.5-fold and a p value of 0.05 or less was required for a difference in signal to be considered statistically significant. When comparing the transcriptional responses of calves infected with the MAA versus MAP, unique patterns of expression were clearly visible. In general, numbers of transcripts altered in response to infection were much greater for MAA-infected animals than for those infected with the MAP. No genes were significantly up-regulated in MAP-infected animals at the earliest time point tested (30 min), and only modest numbers of genes were increased in expression over the experimental time course. On the other hand, up-regulated transcripts were detected by 30 min in MAA-infected animals and peaked by 2 hr. Differences in the numbers of down-regulated genes between MAP-infected and MAA-infected animals (compared to PBS-infected controls) were less pronounced. At the earliest time points, MAP-infected calves had a greater number of down-regulated genes than did animals infected with MAA. This trend was reversed at 8 and 12 hr post-infection. Keywords: Gene expression profiling by microarray Microarrays were used to examine the transcriptional profiles of bovine intestinal mucosa inoculated with PBS, MAP or MAA and across six time points (30 min, 1, 2, 4, 8, and 12 hours). Experiments were performed in quadruplicate for PBS, MAP, and MAA (bovine ligated ileal loops surgeries were performed with four calves). For one surgery, MAA was used for 4 time ponts only, thus generateing a total of 70 arrays.

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Differentially expressed genes in human macrophages infected with clinical isolates of Mycobacterium avium displaying phenotypically and genotypically distinct characteristics

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