Transcriptional profiling of murine organ genes in response to infection with Bacillus anthracis Ames spores

Scott T. Moen, Linsey A. Yeager, William Lawrence, Cindy Ponce, Cristi L. Galindo, Harold R. Garner, Wallace B. Baze, Giovanni Suarez, Johnny Peterson, Ashok Chopra

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Bacillus anthracis is the Gram-positive, spore-forming etiological agent of anthrax, an affliction studied because of its importance as a potential bioweapon. Although in vitro transcriptional responses of macrophages to either spore or anthrax toxins have been previously reported, little is known regarding the impact of infection on gene expression in host tissues. We infected Swiss-Webster mice intranasally with 5 LD50 of B. anthracis-virulent Ames spores and observed the global transcriptional profiles of various tissues over a 48 h time period. RNA was extracted from spleen, lung, and heart tissues of infected and control mice and examined by Affymetrix GeneChip analysis. Approximately 580 host genes were significantly over or under expressed among the lung, spleen, and heart tissues at 8 and 48 h time points. Expression of genes encoding for surfactant and major histocompatibility complex (MHC) presentation was diminished during the early phase of infection in lungs. By 48 h, a significant number of genes were modulated in the heart, including up-regulation of calcium-binding-related gene expression, and down-regulation of multiple genes related to cell adhesion, formation of the extracellular matrix, and the cell cytoskeleton. Interestingly, the spleen 8 h post-infection showed striking increases in the expression of genes that encode hydrolytic enzymes, and these levels remained elevated throughout infection. Further, genes involving antigen presentation and interferon responses were down-regulated in the spleen at 8 h. In late stages of infection, splenic genes related to the inflammatory response were up-regulated. This study is the first to describe the in vivo global transcriptional response of multiple organs during inhalational anthrax. Although numerous genes related to the host immunological response and certain protection mechanisms were up-regulated in these organs, a vast list of genes important for fully developing and maintaining this response were decreased. Additionally, the lung, spleen, and heart showed differential responses to the infection, further validating the demand for a better understanding of anthrax pathogenesis in order to design therapies against novel targets.

Original languageEnglish (US)
Pages (from-to)293-310
Number of pages18
JournalMicrobial Pathogenesis
Volume44
Issue number4
DOIs
StatePublished - Apr 2008

Fingerprint

Bacillus anthracis
Spores
Spleen
Anthrax
Infection
Genes
Lung
Gene Expression
Lethal Dose 50
Antigen Presentation
Gene Expression Regulation
Major Histocompatibility Complex
Cytoskeleton
Cell Adhesion
Surface-Active Agents
Interferons
Extracellular Matrix
Up-Regulation
Down-Regulation
Macrophages

Keywords

  • Affymetrix microarrays
  • Anthrax
  • Bacillus anthracis
  • Murine model of infection

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Transcriptional profiling of murine organ genes in response to infection with Bacillus anthracis Ames spores. / Moen, Scott T.; Yeager, Linsey A.; Lawrence, William; Ponce, Cindy; Galindo, Cristi L.; Garner, Harold R.; Baze, Wallace B.; Suarez, Giovanni; Peterson, Johnny; Chopra, Ashok.

In: Microbial Pathogenesis, Vol. 44, No. 4, 04.2008, p. 293-310.

Research output: Contribution to journalArticle

Moen, Scott T. ; Yeager, Linsey A. ; Lawrence, William ; Ponce, Cindy ; Galindo, Cristi L. ; Garner, Harold R. ; Baze, Wallace B. ; Suarez, Giovanni ; Peterson, Johnny ; Chopra, Ashok. / Transcriptional profiling of murine organ genes in response to infection with Bacillus anthracis Ames spores. In: Microbial Pathogenesis. 2008 ; Vol. 44, No. 4. pp. 293-310.
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