Dataset Information


Transcription profiling by array of human alveolar macrophages infected with Bacillus anthracis spores.

ABSTRACT: Bacillus anthracis is a gram-positive, aerobic, spore-forming, rod-shaped bacterium which has recently been used as an agent of bioterrorism. Because there is a significant delay between the initial contact of the spore with the host and clinical evidence of disease, there appears to be temporary containment of the pathogen by the innate immune system. Contact with the human alveolar macrophage (HAM) plays a key role in the innate immune response to B. anthracis spores. Therefore, the early macrophage response to anthrax exposure is important in understanding the pathogenesis of this disease. The majority of genes modulated by spores were upregulated, and a lesser number were downregulated. The data was subjected to Ingenuity Pathway analysis, the Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, and the Promoter Analysis and Interaction Network Toolset (PAINT). Among the upregulated genes, we identified a group of chemokine ligands, apoptosis genes and, interestingly, keratin filament genes. Central hubs regulating the activated genes were TNF-, NF-κB and their ligands/receptors. Other activated genes included IL-1 and IL-18. RNA for these, and several additional cytokines including IL-6, IL-1, IP-10 and GM-CSF, were differentially expressed from 1.6- to 27-fold. The microarray cytokine data is consistent with our previously published findings which demonstrated that there was 4- to 43-fold induction of these cytokines at the transcriptional and translational levels as determined by RNase protection assays and ELISA. The PAINT analysis revealed that the majority of the genes affected by spores contain the binding site for c-Rel, a member of the NF-κB family of transcription factors. Other transcription regulatory elements contained in many of the upregulated genes were c-Myb, CP2, Barbie Box, E2F and CRE-BP1. This study is the first detailed microarray analysis to describe the HAM response to B. anthracis. Experiment Overall Design: In this paper, we exposed HAM to B. anthracis Sterne spores at an MOI of 1 for 6 hours. RNA was extracted from HAM and analyzed by the Affymetrix Human Genome U133 Plus 2.0 Array. The transcriptional profile of Bacillus anthracis spore-treated HAM was compared with mock infected cells, and differentially expressed genes were identified.


INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens  

SUBMITTER: Mikhail Dozmorov  

PROVIDER: E-GEOD-14390 | ArrayExpress | 2009-10-16



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Gene expression profiling of human alveolar macrophages infected by B. anthracis spores demonstrates TNF-alpha and NF-kappab are key components of the innate immune response to the pathogen.

Dozmorov Mikhail M   Wu Wenxin W   Chakrabarty Kaushik K   Booth J Leland JL   Hurst Robert E RE   Coggeshall K Mark KM   Metcalf Jordan P JP  

BMC infectious diseases 20090910

Bacillus anthracis, the etiologic agent of anthrax, has recently been used as an agent of bioterrorism. The innate immune system initially appears to contain the pathogen at the site of entry. Because the human alveolar macrophage (HAM) plays a key role in lung innate immune responses, studying the HAM response to B. anthracis is important in understanding the pathogenesis of the pulmonary form of this disease.In this paper, the transcriptional profile of B. anthracis spore-treated HAM was compa  ...[more]

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