Gene expression profiling of human alveolar macrophages infected by B. anthracisspores demonstrates TNF-α and NF-κb are key components of the innate immune response to the pathogenReport as inadecuate




Gene expression profiling of human alveolar macrophages infected by B. anthracisspores demonstrates TNF-α and NF-κb are key components of the innate immune response to the pathogen - Download this document for free, or read online. Document in PDF available to download.

BMC Infectious Diseases

, 9:152

First Online: 10 September 2009Received: 30 April 2009Accepted: 10 September 2009

Abstract

BackgroundBacillus 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.

MethodsIn this paper, the transcriptional profile of B. anthracis spore-treated HAM was compared with that of mock-infected cells, and differentially expressed genes were identified by Affymetrix microarray analysis. A portion of the results were verified by Luminex protein analysis.

ResultsThe majority of genes modulated by spores were upregulated, and a lesser number were downregulated. The differentially expressed genes were subjected to Ingenuity Pathway analysis, the Database for Annotation, Visualization and Integrated Discovery DAVID analysis, the Promoter Analysis and Interaction Network Toolset PAINT and Oncomine analysis. Among the upregulated genes, we identified a group of chemokine ligand, apoptosis, and, interestingly, keratin filament genes. Central hubs regulating the activated genes were TNF-α, NF-κB and their ligands-receptors. In addition to TNF-α, a broad range of cytokines was induced, and this was confirmed at the level of translation by Luminex multiplex protein analysis. PAINT analysis revealed that many 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. However, many of the genes are poorly annotated, indicating that they represent novel functions. Four of the genes most highly regulated by spores have only previously been associated with head and neck and lung carcinomas.

ConclusionThe results demonstrate not only that TNF-α and NF-κb are key components of the innate immune response to the pathogen, but also that a large part of the mechanisms by which the alveolar macrophage responds to B. anthracis are still unknown as many of the genes involved are poorly annotated.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2334-9-152 contains supplementary material, which is available to authorized users.

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Author: Mikhail Dozmorov - Wenxin Wu - Kaushik Chakrabarty - J Leland Booth - Robert E Hurst - K Mark Coggeshall - Jordan P Met

Source: https://link.springer.com/



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