Abstract
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.
Highlights
Mycobacterium tuberculosis (Mtb) causes most cases of tuberculosis (TB) in humans, claiming over 1.5 million lives every year
To evaluate the possibility of whether the genetic diversity of the strains could instead be explained by function-specific differences in host cells, we performed the sample classifications with the same parameters to Figure 2A but using genes only annotated to specific functional categories
The host transcriptome responses induced by H37Rv and by different sublineages of Mtb W-Beijing strains are predominantly similar, and hardly broad differences as well as immune responsespecific differences were detectable, even though we can not guarantee that minor differences would be observed if more biological replicates were involved
Summary
Mycobacterium tuberculosis (Mtb) causes most cases of tuberculosis (TB) in humans, claiming over 1.5 million lives every year. Mtb lineages are named after their geographic origins. One group of such genetically related Mtb isolates was first reported from patients mainly from Beijing, China, and was named as ‘‘Beijing family’’ of Mtb strains [4]. At the same time period, ‘‘W’’ strains were described in New York City, USA [5], and exhibited relatedness with strains of the Beijing family [6]. These two strain families were collectively named as ‘‘W-Beijing’’
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
