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Microarray analysis of mRNA levels from RAW264.7 macrophages infected with Brucella abortus. Infect Immun 2003 Mar;71(3):1125-33

Date

02/22/2003

Pubmed ID

12595423

Pubmed Central ID

PMC148819

DOI

10.1128/IAI.71.3.1125-1133.2003

Scopus ID

2-s2.0-0037369742   88 Citations

Abstract

Identification of host responses at the gene transcription level provides a molecular profile of the events that occur following infection. Brucella abortus is a facultative intracellular pathogen of macrophages that induces chronic infection in humans and domestic animals. Using microarray technology, the response of macrophages 4 h following B. abortus infection was analyzed to identify early intracellular infection events that occur in macrophages. Of the >6,000 genes, we identified over 140 genes that were reproducibly differentially transcribed. First, an increase in the transcription of a number of proinflammatory cytokines and chemokines, such as tumor necrosis factor alpha, interleukin-1beta (IL-1beta), IL-1alpha, and members of the SCY family of proteins, that may constitute a general host recruitment of antibacterial defenses was evident. Alternatively, Brucella may subvert newly arriving macrophages for additional intracellular infection. Second, transcription of receptors and cytokines associated with antigen presentation, e.g., major histocompatibility complex class II and IL-12p40, were not evident at this 4-h period of infection. Third, Brucella inhibited transcription of various host genes involved in apoptosis, cell cycling, and intracellular vesicular trafficking. Identification of macrophage genes whose transcription was inhibited suggests that Brucella utilizes specific mechanisms to target certain cell pathways. In conclusion, these data suggest that B. abortus can alter macrophage pathways to recruit additional macrophages for future infection while simultaneously inhibiting apoptosis and innate immune mechanisms within the macrophage, permitting intracellular survival of the bacterium. These results provide insights into the pathogenic strategies used by Brucella for long-term survival within a hostile environment.

Author List

Eskra L, Mathison A, Splitter G

Author

Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Brucella abortus
Cell Line
Macrophages
Mice
Oligonucleotide Array Sequence Analysis
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction