Previous Article | Next Article ![]()
Infection and Immunity, January 2004, p. 498-507, Vol. 72, No. 1
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.1.498-507.2004
Copyright © 2004, American
Society for
Microbiology. All Rights Reserved.
Departments of Pathology and Microbiology and Immunology,1 UTMB Bioinformatics Program and the Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston, Texas 775552
Received 1 July 2003/ Returned for modification 12 September 2003/ Accepted 29 September 2003
Ehrlichia
chaffeensis is an obligatory intracellular bacterium which resides
in an early endosome in monocytes. E. chaffeensis
infection in a human monocyte cell line (THP1) significantly altered
the transcriptional levels of 4.5% of host genes, including
those coding for apoptosis inhibitors, proteins regulating cell
differentiation, signal transduction, proinflammatory cytokines,
biosynthetic and metabolic proteins, and membrane trafficking proteins.
The transcriptional profile of the host cell revealed key themes in the
pathogenesis of Ehrlichia. First, E. chaffeensis
avoided stimulation of or repressed the transcription of cytokines
involved in the early innate immune response and cell-mediated immune
response to intracellular microbes, such as the interleukin-12 (IL-12),
IL-15, and IL-18 genes, which might make Ehrlichia a stealth
organism for the macrophage. Second, E. chaffeensis
up-regulated NF-
B and apoptosis inhibitors and differentially
regulated cell cyclins and CDK expression, which may enhance host cell
survival. Third, E. chaffeensis also inhibited the gene
transcription of RAB5A, SNAP23, and STX16, which are involved in
membrane trafficking. By comparing the transcriptional response of
macrophages infected with other bacteria and that of macrophages
infected with E. chaffeensis, we have identified few genes
that are commonly induced and no commonly repressed genes. These
results illustrate the stereotyped macrophage response to other
pathogens, in contrast with the novel host response to obligate
intracellular Ehrlichia, whose survival depends entirely on a
long evolutionary process of outmaneuvering
macrophages.
This article has been cited by other articles:
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»