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. 2004 Jan;72(1):498-507.
doi: 10.1128/IAI.72.1.498-507.2004.

Survival strategy of obligately intracellular Ehrlichia chaffeensis: novel modulation of immune response and host cell cycles

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Survival strategy of obligately intracellular Ehrlichia chaffeensis: novel modulation of immune response and host cell cycles

Jian-zhi Zhang et al. Infect Immun. 2004 Jan.

Abstract

Ehrlichia chaffeensis is an obligatory intracellular bacterium which resides in an early endosome in monocytes VSports手机版. 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-kappaB 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. .

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Figures

FIG. 3.
FIG. 3.
Repression of transcription of IL-15 and IL-18 genes by E. chaffeensis.
FIG. 1.
FIG. 1.
Reproducibility of the oligonucleotide array. The average differences for the data at 0 h (A) and 11 h (B) from experiment 1 versus the corresponding time course for experiment 2 were plotted by pairwise comparisons. The only criterion for inclusion was that the probe set was designated “present” in both time series. Least-square linear regression was used to determine the fit to a straight line. For the 0-h data set, the regression was described by the equation y = 1.172 x − 715.408 (r2 = 0.935), and for the 36-h data set, the equation was y = 1.198x − 741.671 (r2 = 0.911).
FIG. 2.
FIG. 2.
Hierarchical cluster analysis of 570 genes with threefold changes after exposure to E. chaffeensis. T00, T01, T11, and T24 represented 0, 1, 7, 11, and 24 h postinoculation. Z-score values are displayed colorimetrically from top to bottom. Line lengths in the dendrogram indicate the correlation of the genes, with shorter lines indicating higher levels of correlation. Genes induced by E. chaffeensis are indicated in red, and genes with reduced expression are indicated in green. The degree of redness represents the level of induction, whereas that of greenness represents the level of repression. Each column presents the expression of that gene at the indicated time point relative to uninfected THP1 cells. The complete data set was deposited at http://www.bioinfo.utmb.edu.
FIG. 4.
FIG. 4.
Regulation of gene transcription of proteins involved in vesicle docking by E. chaffeensis.
FIG. 5.
FIG. 5.
Differential regulation of gene transcription of apoptosis inhibitors and inducers by E. chaffeensis.
FIG. 6.
FIG. 6.
Differential regulation of gene transcription of proteins involved in the cell cycle by E. chaffeensis.

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