Diverse infection models demonstrate robust resistance of Mycobacterium tuberculosis to innate immunity
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE328967 | GEO | 2026/05/31
REPOSITORIES: GEO
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Project description:Host cell metabolic pathways influence innate immune responses to intracellular pathogens, but the contribution of nucleotide metabolism to antimicrobial defense remains incompletely defined. Here, we identify the mitochondrial nucleoside monophosphate kinase CMPK2 as a regulator of macrophage responses to Mycobacterium tuberculosis (Mtb). Using a targeted genetic screen of candidate host factors, we found that depletion of CMPK2 enhances intracellular Mtb replication in human macrophages. This phenotype was confirmed using both shRNA-mediated knockdown and CRISPR-Cas9-mediated knockout approaches. CMPK2 expression increased following macrophage activation and Mtb infection. Transcriptomic profiling revealed that loss of CMPK2 is associated with broad alterations in gene expression, including reduced expression of genes linked to innate immune and inflammatory responses early after infection. In contrast, myeloid-specific deletion of Cmpk2 in mice did not significantly alter bacterial burden or survival following aerosol Mtb infection, indicating that the contribution of CMPK2 to host defense is context dependent. Together, these findings identify CMPK2 as a host factor that limits Mtb replication in human macrophages and shapes innate immune gene expression programs.
2026-05-15 | GSE331078 | GEO
Project description:Mycobacterium tuberculosis (Mtb) cultured in the absence of detergent forms biofilm-like cords, a clinical identifier of virulence. Using lung-on-chip and mouse infection models, we show that cord growth in alveolar cells contributes to the suppression of innate immune signalling via nuclear compression. Thereafter, extracellular cords cause contact-dependent phagocyte death but grow intercellularly between epithelial cells. These “mechanopathological” mechanisms explain the greater proportion of alveolar lesions with increased immune infiltration and dissemination defects in cording-deficient Mtb infections. Compression of WT Mtb lipid monolayers induces a phase transition that enables mechanical energy storage. Agent-based simulations demonstrate that the increased energy storage capacity is sufficient for the formation of stable cords that maintain structural integrity despite mechanical perturbation. Moreover, bacteria in cords remain translationally active despite prolonged antibiotic exposure and regrow rapidly upon cessation of treatment. This study provides a conceptual framework for the biophysics of cord architectures and their functional roles in tuberculosis infection and therapy, independent of mechanisms ascribed to single bacteria.
2023-11-01 | GSE238102 | GEO
Project description:Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health burden, characterized by complex host–pathogen interactions that drive heterogeneous clinical outcomes. While pulmonary epithelial cells are increasingly recognized as active participants in innate immunity during Mtb infection, how host defences are altered when the epithelial barrier is compromised remains unclear . In this study, we developed a murine model combining naphthalene-induced airway epithelial injury with Mtb infection, and found a pronounced impairment in pulmonary bacterial clearance. Through single-cell RNA sequencing (scRNA-seq), we mapped the pulmonary cells landscape and identified widespread suppression of epithelial immune functions. Notably, we observed macrophages transition from an antimicrobial to an antigen-presenting phenotype, indicating waning pulmonary innate defenses and heightened adaptive immune activation. These findings highlight the pivotal role of pulmonary epithelial integrity in shaping host immunity against Mtb and offer new insights into potential therapeutic strategies targeting barrier–immune crosstalk.
2025-11-18 | GSE298041 | GEO
Project description:Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection. Mice were infected with Mtb and treatment with PZA was started at 28 days post-infection. At 42 days and 63 days post-infection, group of animals were euthanized and lung tissue was collected to isolate total RNA and used in microarray experiments. Mtb-infected, untreated animals served as controls.
2013-06-28 | E-GEOD-48027 | biostudies-arrayexpress
Project description:Diverse infection models demonstrate robust resistance of Mycobacterium tuberculosis to innate immunity
| PRJNA1457103 | ENA
Project description:Mycobacterium tuberculosis (Mtb) is one of the most successful pathogens in human history and remains the second leading cause of death from an infectious agent worldwide. The major reason of Mtb success principally relies on its ability to perfectly adapt to the host, by establishing latent infection and evading from the control driven by immune system. Accordingly, both innate and adaptive immune responses are required to control TB progression and pathogenesis and in particular dendritic cells (DC), as professional antigen presenting cells, are one of the major cellular effectors of the anti-mycobacterial response. In this context, we performed a microarray analysis to characterize the de-regulation of cellular miRNAs during Mtb infection of human DC. Human DC were prepared from human peripheral blood mononuclear cells of anonymous healthy blood donors and infected with Mtb for 3, 8 and 24 hours. This data set contains the global miRNA expression profiling in uninfected and Mtb-infected DC cultures to identify altered signature of miRNAs potentially implicated in Mtb-mediated immune evasion strategies.
2017-12-12 | E-MTAB-6083 | biostudies-arrayexpress
Project description:Crosstalk between autophagy, host cell death, and inflammatory host responses to bacterial pathogens enables effective innate immune responses that limit bacterial growth while reducing coincidental host damage. Mycobacterium tuberculosis thwarts innate immune defense mechanisms in alveolar macrophages (AMs) during the initial stages of infection and in recruited bone marrow-derived cells during later stages of infection. How protective inflammatory responses are achieved during Mycobacterium tuberculosis (Mtb) infection and the differences in these responses in macrophage subtypes are obscure. Here, we discovered that the autophagy receptor Tax1bp1 plays a critical role in enhancing inflammatory cytokine production and promoting the susceptibility of mice to infection with Mtb. These results were surprising because Tax1bp1 instead restricts Mtb growth during infection of bone marrow-derived macrophages (BMDMs), as we previously showed (Budzik et al. 2020), and terminates cytokine production in response to cytokine stimulation or viral infection. Tax1bp1 also leads to increases in bacterial growth and inflammatory responses during infection of mice with Listeria monocytogenes, an intracellular pathogen that is not effectively targeted to canonical autophagy. In contrast to its role in restricting Mtb growth in BMDMs, Tax1bp1 promotes Mtb growth in AMs, neutrophils, and recruited monocyte-derived cells from the bone marrow. In Mtb-infected AMs, Tax1bp1 enhances necrosis and inflammatory cytokine synthesis while restraining apoptosis, changing the mode of host cell death to favor Mtb replication. Similar to Tax1bp1-deficiency in AMs, the expression of phosphosite-deficient Tax1bp1 restricts Mtb growth. Together, these results show that Tax1bp1 plays a crucial role in linking the regulation of autophagy, cell death, and pro-inflammatory host responses to augment susceptibility to bacterial infection.
2025-02-12 | GSE280399 | GEO
Project description:Innate immune cells such as monocytes and macrophages provide the earliest defense against infection by intracellular pathogens by initiating signaling pathways and restricting pathogen replication. However, the full complement of proteins that mediate cell-autonomous immunity remains incompletely defined. Here, we applied cysteine-directed activity-based protein profiling (ABPP) to map proteome-wide cysteine reactivity changes in THP-1 monocytes and primary human monocyte-derived macrophages during Mycobacterium tuberculosis (Mtb) infection. Across both cell types, we quantified 148 cysteine residues with altered reactivity. Genetic perturbation of a subset of proteins harboring these changes significantly impacted Mtb replication, revealing functional links between site-specific cysteine reactivity and antimicrobial defense. These data define previously unrecognized host protein changes during Mtb infection and provide a resource for investigating post-translational events that regulate innate immune responses to intracellular bacteria.
2026-03-02 | PXD067709 | Pride
Project description:Extracellular vesicles (EVs) secreted by Mtb-infected macrophages (MΦEVMtb) may influence the host innate immune response to Mtb-infection, but specific EV-induced mechanisms that regulate such cell phenotype changes are not yet known. We report that PMBCs cultured with MΦEVMtb exhibit a marked classical to intermediate monocyte polarization effect, as detected by single-cell RNA sequencing and flow cytometry results. Moreover, this effect appears to correspond with the activation of the alternative NF-κB pathway, and can be partially recapitulated by treating PBMCs with EV derived from recombinant cell line that overexpresses TRAF1, a direct regulator of this pathway. Collectively, we depict an EV-mediated monocyte reprogram landscape in the context of Mtb infection and highlight a potential link between EV and pathogenesis of tuberculosis.
2026-06-30 | GSE269069 | GEO
Project description:Mycobacterium tuberculosis(Mtb) is known to reside in cells of innate immune system- macrophages and dendritic cells. A variety of non -conventional cell typeslike adipocytes, mesenchyal stem cells and osteoclasts can also be infected with Mtb. However, cellular transcriptional adapations enabling survival of Mtb in these cells remain known. We used microarrays to understand global changes in transcriptional profiling during macrophage to osteoclast transition in presence of Mycobacterium tuberculosis.
2016-08-15 | GSE61531 | GEO