Comparative transcriptomic analysis of THP‐1‐derived macrophages infected with <i>Mycobacterium tuberculosis</i> H37Rv, H37Ra and BCG

Pu, Wenyuan; Zhao, Chen; Wazir, Junaid; Su, Zhonglan; Niu, Mengyuan; Song, Shiyu; Wei, Lulu; Li, Li; Zhang, Xia; Shi, Xudong; Wang, Hongwei

doi:10.1111/jcmm.16980

Cited by 29 publications

(20 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We determined that there were significantly more genes that were upregulated than downregulated upon Mtb infection in macrophages. This is consistent with previous transcriptome analyses of Mtb infected macrophages (Wu et al 2012;Seshadri et al 2017;Papp et al 2018;Roy et al 2018;Lee et al 2019;Looney et al 2021;Pu et al 2021). We also found that there was almost an equal number of DAR where CA increased or decreased upon Mtb infection in macrophages.…”

Section: Discussionsupporting

confidence: 93%

“…Considering that they infected with MOI 5, the parallel number of DAR and DEG is still significantly less than reported in our study. Given that multiple studies in addition to ours report between 600 and 3000 DEG in macrophages upon Mtb infection using these standard cutoffs (Wu et al 2012;Seshadri et al 2017;Papp et al 2018;Roy et al 2018;Lee et al 2019;Looney et al 2021;Pu et al 2021), it appears as though there may be a limiting factor in the data reported by Correa-Macedo et al. This may be due to the phenotypic and functional differences between hAM and THP-1 cells, conditions of Mtb infection (MOI, time, strain), or variability between patient samples caused by increased genomic heterogeneity.…”

Section: Discussionmentioning

confidence: 49%

“…2019; Looney et al . 2021; Pu et al . 2021), it appears as though there may be a limiting factor in the data reported by Correa-Macedo et al.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Transcriptome and chromatin accessibility mapping reveals a type I Interferon response triggered by Mycobacterium tuberculosis infection

Madden

Hamra

Berton

et al. 2022

Preprint

View full text Add to dashboard Cite

Tuberculosis, a deadly infectious lung disease caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of bacterial disease-related deaths worldwide. The success of Mtb as a human pathogen depends on its ability to manipulate host immune response pathways, many of which are regulated by epigenetic mechanisms that control the accessibility of chromatin to the transcriptional machinery. Recent reports suggest that host phosphatases, such as PPM1A, may play a role in the regulation of chromatin accessibility during bacterial infections. However, changes in genome-wide chromatin accessibility during Mtb infection and whether PPM1A plays a role in this process remains unknown. Using combinatorial chromatin accessibility (ATAC-seq) and transcriptomics (RNA-seq) profiling of wild-type (WT), PPM1A knockout (ΔPPM1A) and PPM1A overexpressing (PPM1A+) macrophages, we demonstrate that Mtb infection induces global chromatin remodeling consistent with changes in gene expression signatures. The strongest concordant chromatin accessibility and gene expression signature triggered by Mtb infection was enriched for genes involved in the type I interferon (IFN) signaling pathways. Modulation of PPM1A expression results in altered chromatin accessibility signatures during Mtb infection that are reflected in the total number, chromosome location and directionality of change. Transcription factor motif analysis revealed an enrichment for transcription factors involved in the type I IFN pathway during Mtb infection, including IRF4, MEF2A, CEBPD and JDP2. In contrast, both deletion and overexpression of PPM1A produced unique transcription factor enrichment signatures linked to the genomic regions with altered chromatin accessibility. Our study demonstrates that altered type I IFN responses in Mtb-infected macrophages occurs as a result of genome-wide changes in chromatin accessibility, and that PPM1A likely plays a role in a subset of these signatures.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 49%

See 1 more Smart Citation

Transcriptome and chromatin accessibility mapping reveals a type I Interferon response triggered by Mycobacterium tuberculosis infection

Madden

Hamra

Berton

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In our previous work, mice were infected intravenously with attenuated strain H37Ra and virulent strain H37Rv, and we found that there were no significant differences in immune responses and bacteria burdens between the two strains within at least 8 w ( Ning et al., 2017 ). Although studies have shown that macrophages infected with H37Ra and H37Rv respectively produced distinct cellular transcriptomic changes, ( Pu et al., 2021 ), proteome levels of macrophages infected with H37Ra or H37Rv respectively showed very little expression difference in log and stationary phase, indicating H37Ra was able to induce a similar immune response with H37Rv ( Wang et al., 2021 ). Thus, in this study the attenuated M. tuberculosis strain H37Ra was used instead of H37Rv to construct an intranasal infection model, which simulated the natural process of pulmonary infection similar to aerosol pathway ( Logan et al., 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice

Ning²,

Kang³

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Many antigens from Mycobacterium tuberculosis (M. tuberculosis) have been demonstrated as strong immunogens and proved to have application potential as vaccine candidate antigens. Cyclic di-AMP (c-di-AMP) as a bacterial second messenger regulates various bacterial processes as well as the host immune responses. Rv2837c, the c-di-AMP phosphodiesterase (CnpB), was found to be relative to virulence of M. tuberculosis and interference with host innate immune response. In this study, recombinant CnpB was administered subcutaneously to mice. We found that CnpB had strong immunogenicity and induced high levels of humoral response and lung mucosal immunity after M. tuberculosis intranasally infection. CnpB immunization stimulated splenocyte proliferation and the increasing number of activated NK cells but had little effects on Th1/Th2 cellular immune responses in spleens. However, CnpB induced significant Th1/Th2 cellular immune responses with a decreased number of T and B cells in the lungs, and significantly recruits of CD4+ and CD8+ T cells after M. tuberculosis attenuated strain H37Ra infection. Besides, we first reported that CnpB could stimulate IFN-β expression transitorily and inhibit the autophagy of macrophages in vitro. In mice intranasally infection model, CnpB immunization alleviated pathological changes and reduced M. tuberculosis H37Ra loads in the lungs. Thus, our results suggested that CnpB interferes with host innate and adaptive immune responses and confers protection against M. tuberculosis respiratory infection, which should be considered in vaccine development as well as a drug target.

show abstract

“…The difference in phenotype induced by virulent and avirulent strains is an effective approach to explore TB pathogenesis. Previous studies showed that, in the virulent MTB strain H37Rv-infected macrophages, 36 genes related to immune response regulation, chemokine secretion, and leucocyte chemotaxis were upregulated, and 30 genes associated with amino acid biosynthetic and energy metabolism, connective tissue development, and extracellular matrix organization were downregulated, compared to avirulent strain-infected macrophage [ 14 ]. Virulent M. bovis and BCG can also lead to different immune responses associated with TB pathogenesis [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Unique Key miRNAs, TFs, and mRNAs in Virulent MTB Infection Macrophages by Network Analysis

Zhu

Liu

et al. 2021

IJMS

View full text Add to dashboard Cite

Although Mycobacterium tuberculosis (MTB) has existed for thousands of years, its immune escape mechanism remains obscure. Increasing evidence signifies that microRNAs (miRNAs) play pivotal roles in the progression of tuberculosis (TB). RNA sequencing was used to sequence miRNAs in human acute monocytic leukemia cells (THP-1) infected by the virulent MTB-1458 strain and the avirulent vaccine strain Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Sets of differentially expressed miRNAs (DE-miRNAs) between MTB-1458/BCG-infected groups and uninfected groups were identified, among which 18 were differentially expressed only in the MTB-1458-infected THP-1 group. Then, 13 transcription factors (TFs) and 81 target genes of these 18 DE-miRNAs were matched. Gene Ontology classification as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the candidate targets were predominantly involved in apoptotic-associated and interferon-γ-mediated signaling pathways. A TF-miRNA-mRNA interaction network was constructed to analyze the relationships among these 18 DE-miRNAs and their targets and TFs, as well as display the hub miRNAs, TFs, and target genes. Considering the degrees from network analysis and the reported functions, this study focused on the BHLHE40-miR-378d-BHLHE40 regulation axis and confirmed that BHLHE40 was a target of miR-378d. This cross-talk among DE-miRNAs, mRNAs, and TFs might be an important feature in TB, and the findings merited further study and provided new insights into immune defense and evasion underlying host-pathogen interactions.

show abstract

Comparative transcriptomic analysis of THP‐1‐derived macrophages infected with Mycobacterium tuberculosis H37Rv, H37Ra and BCG

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 29 publications

References 35 publications

Transcriptome and chromatin accessibility mapping reveals a type I Interferon response triggered by Mycobacterium tuberculosis infection

Transcriptome and chromatin accessibility mapping reveals a type I Interferon response triggered by Mycobacterium tuberculosis infection

Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice

Identification of Unique Key miRNAs, TFs, and mRNAs in Virulent MTB Infection Macrophages by Network Analysis

Contact Info

Product

Resources

About