Details:

Alternative Title:
PLoS One
Personal Author:
Wu, Kang; Dong, Dandan; Fang, Hai; Levillain, Florence; Jin, Wen; ... More +
Wu, Kang; Dong, Dandan; Fang, Hai; Levillain, Florence; Jin, Wen; Mei, Jian; Gicquel, Brigitte; Du, Yanzhi; Wang, Kankan; Gao, Qian; Neyrolles, Olivier; Zhang, Ji; Less -
Description:
The W-Beijing family of Mycobacterium tuberculosis (Mtb) strains is known for its high-prevalence and -virulence, as well as for its genetic diversity, as recently reported by our laboratories and others. However, little is known about how the immune system responds to these strains. To explore this issue, here we used reverse engineering and genome-wide expression profiling of human macrophage-like THP-1 cells infected by different Mtb strains of the W-Beijing family, as well as by the reference laboratory strain H37Rv. Detailed data mining revealed that host cell transcriptome responses to H37Rv and to different strains of the W-Beijing family are similar and overwhelmingly induced during Mtb infections, collectively typifying a robust gene expression signature ("THP1r2Mtb-induced signature"). Analysis of the putative transcription factor binding sites in promoter regions of genes in this signature identified several key regulators, namely STATs, IRF-1, IRF-7, and Oct-1, commonly involved in interferon-related immune responses. The THP1r2Mtb-induced signature appeared to be highly relevant to the interferon-inducible signature recently reported in active pulmonary tuberculosis patients, as revealed by cross-signature and cross-module comparisons. Further analysis of the publicly available transcriptome data from human patients showed that the signature appears to be relevant to active pulmonary tuberculosis patients and their clinical therapy, and be tuberculosis specific. Thus, our results provide an additional layer of information at the transcriptome level on mechanisms involved in host macrophage response to Mtb, which may also implicate the robustness of the cellular defense system that can effectively fight against genetic heterogeneity in this pathogen.
Subject:
[+]
Biology
Cell Line
Gene Expression Profiling
Humans
Inflammation
Interferon Regulatory Factors
Interferons
Macrophages
Medicine
Mycobacterium Tuberculosis
Reproducibility Of Results
Research Article
Reverse Transcriptase Polymerase Chain Reaction
Species Specificity
STAT Transcription Factors
Transcription, Genetic
Transcription Factors
Transcriptome
Tuberculosis

Source:
PLoS One. 2012; 7(6).;
Document Type:
Journal Article;
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:cd450745993dbe76fde28bc0a1076938cb79353e8193139809e63c04622c1849
File Type:

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