Survival strategy of obligately intracellular Ehrlichia chaffeensis: novel modulation of immune response and host cell cycles.
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-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.
Zhang
Jian-zhi
JZ
Departments of Pathology and Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas 77555, USA.
Sinha
Mala
M
Luxon
Bruce A
BA
Yu
Xue-jie
XJ
D017209:Apoptosis; D002460:Cell Line; D018469:Ehrlichia chaffeensis / Q000254:growth & development* / Q000472:pathogenicity*; D016873:Ehrlichiosis / Q000276:immunology* / Q000382:microbiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000382:microbiology* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D015345:Oligonucleotide Probes; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015345:Oligonucleotide Probes; D011506:Proteins