Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Adaptive immunity shapes baseline pImmunity Shapes Baseline Physiology of M. Tuberculosistuberculosis in High-Dose Versus Low-Dose I in high-dose versus low-dose infection BALB/c mouse drug treatment mMouse Drug Treatment Models

ABSTRACT: Around day 16 of infection with Mycobacterium tuberculosis (Mtb), the BALB/c mouse adaptive immunity activates to combat the infection. Usual dual RNA-seq, we investigated the transcriptional changes that occur in both mouse host and Mtb pathogen during an untreated low dose aerosol (LDA) infection—focusing on the transition from innate to adaptive immunity. We found that the onset of adaptive immunity coincided with a rapid reprogramming of Mtb physiology, characterized by suppressed respiration, metabolism, and biosynthesis, together with induction of stress and nutrient acquisition pathways. Changes in key Mtb processes were concordant with changes in host expression of canonical features of adaptive immunity.

ORGANISM(S): Mus musculus Mycobacterium tuberculosis str. Erdman = ATCC 35801

PROVIDER: GSE324037 | GEO | 2026/07/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Ultra-low dose aerosol infection provides an improved murine model of tuberculosis

Project description:Tuberculosis (TB) is a heterogeneous disease manifesting in a subset of individuals infected with aerosolized Mycobacterium tuberculosis (Mtb). Unlike human TB, murine infection results in uniformly high lung bacterial burdens and poorly organized granulomas. To develop a TB model that more closely resembles human disease, we infected mice with an ultra-low dose (ULD) of between 1-3 founding bacteria, reflecting a physiologic inoculum. ULD-infected mice exhibited highly heterogeneous bacterial burdens, well-circumscribed granulomas that shared features with human granulomas, and prolonged Mtb containment with unilateral pulmonary infection in some mice. We identified blood RNA signatures in mice infected with an ULD or a conventional Mtb dose (50-100 CFU) that correlated with lung bacterial burdens and predicted Mtb infection outcomes across species, including risk of progression to active TB in humans. Overall, these findings highlight the potential of the mouse TB model and show that ULD infection recapitulates key features of human TB.

2020-11-06 | GSE158807 | GEO

Comparative transcriptomic analysis of human macrophages during Mycobacterium avium versus Mycobacterium tuberculosis infection

Project description:The treatment of Mycobacterium avium (Mav) infection, responsible for over 80% of non-tuberculous mycobacterial pulmonary disease, remains challenging due to rising antibiotic resistance and unsatisfactory success rates. Hence, there is a need for a deeper understanding of host–pathogen interactions to inform the development of alternative therapeutic approaches, like host-directed therapy (HDT), aimed at improving host antimycobacterial defenses.. However, compared to Mycobacterium tuberculosis (Mtb) infections, knowledge of host-pathogen interactions for Mav infection is still limited. To address this knowledge gap, we performed a genome-wide host transcriptomic analysis of Mav-infected primary human macrophages —the primary host cell—alongside Mtb-infected macrophages to leverage insights from Mtb research. Our findings show substantial overlap in the gene expression patterns between Mav-infected and Mtb-infected macrophages, including induction of cytokine responses and modulation of various G-protein coupled receptors (GPCRs) involved in (lipid-mediated) macrophage immune functions. Notable differences were observed in nerve growth factor (NGF) signaling and genes of the GTPase of immunity-associated protein (GIMAP) family. This study laid a foundation for identifying both shared and Mav‑specific host response pathways, providing direction for future investigations into host-pathogen interactions during Mav infection and the identification of novel targets for HDT.

2026-01-16 | E-MTAB-15473 | biostudies-arrayexpress

Mycobacterium tuberculosis produces D-serine under hypoxia to limit CD8+ T cell-dependent immunity in mice

Project description:Interferon (IFN)-γ-producing CD8+ T cells are involved in control of Mycobacterium tuberculosis (Mtb) infection, in part by promoting antimicrobial activities of macrophages. Whether Mtb counters these responses, particularly during the hypoxic conditions that arise within granulomas during infection, remains unknown. Using metabolomic, proteomic and genetic approaches, here we show that Mtb induces Rv0884c (SerC), a Mtb phosphoserine aminotransferase, to produce D-serine. This activity increased Mtb pathogenesis in mice but did not directly affect intramacrophage Mtb survival. Instead, D-serine inhibited IFN-γ production by CD8+ T cells, which indirectly reduced the ability of macrophages to restrict Mtb upon coculture. Mechanistically, D-serine interacted with WDR24, a subunit of GATOR2, and inhibited mTORC1 activation in T cells. This decreased T-bet transcription factor expression by CD8+ T cells and reduced IFN-γ production. Our findings suggest a mechanism of mycobacterial metabolic adaptation to hypoxia which leads to amino acid-dependent suppression of adaptive anti-TB immunity.

2024-08-10 | PXD050258 | Pride

Pulmonary Epithelial Injury Impairs Innate Defense and Reprograms Macrophage Function, Reducing Early Mycobacterium tuberculosis Clearance

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

Cholesterol unlinks innate-adaptive immune axis in tuberculosis granulomas [mouse]

Project description:Chronic lung infection, a long-standing global health issue, associates with compromised protective immunity against pathogens (PMID: 29062070, PMID: 27890913). Lung granulomas, consisting of immune cell aggregates, represent regional immune microenvironments formed in response to chronic infections, such as Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB) (PMID: 36493751). However, the microenvironmental factors and mechanisms modulating protective immune response in granulomas remain incompletely understood. Here, we employ multiplex immunohistochemistry and spatial transcriptomics of human specimens and mouse models to map the locations, transcriptomes, and interactions of macrophages and T cells in TB granulomas. We identify the immune plasticity of macrophages and T cells shaped by granuloma lesion severity and their proximity to multinucleated giant cells or tertiary lymphoid structures. We further uncover a lipid-related disruption of innate-adaptive immune interplay in necrotic granulomas, with immunopathological features distinct from those of the lung tumor microenvironment. Mechanistically, this immune disruption results from Mtb-induced macrophage lysosomal cholesterol accumulation, which sequesters major histocompatibility complex II in lysosomes, thereby hindering antigen presentation and impairing T cell anti-Mtb response. Pharmacologically restoring cholesterol homeostasis of lung macrophages enhances T cell anti-Mtb protective immunity in mice. Collectively, our study reveals the lysosomal cholesterol overload-impaired innate-adaptive immune axis in granulomas, and indicates a cholesterol-targeting therapeutic strategy against chronic lung infection.

2026-02-21 | GSE285852 | GEO

Cholesterol unlinks innate-adaptive immune axis in tuberculosis granulomas [human]

2026-02-21 | GSE285046 | GEO

Low Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy

Project description:The development of approaches for inflaming cold tumors is critical for increasing response to immunotherapy. Here we report that low-dose radiotherapy (LDRT) in mice promotes tumor T-cell inflammation and enables responsiveness to combinatorial immunotherapyin an interferon-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity, and depended on both cytotoxic CD4+and CD8+T cells. LDRTinduced predominantly CD4+cells which exhibited features of exhausted effector and cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, and a novel subset of dendritic cells with activated phenotype that expressed the NKG2D ligand Rae1. Finally, tumor immune rejection was critically dependent on the NKG2D pathway. We translated these findings toa phase I clinical trial. Like in mice, combinatorial treatmenttriggered peripheral T-cell mobilization and resulted in important tumor T-cell infiltration, predominantly of CD4+cells and with Th1 signatures, observed only in patients with immune desert tumors who responded to a novel combination of LDRT, low dose cyclophosphamide and immune checkpoint blockade therapy.These results suggest the novel possibility of rationally combining LDRT with immune checkpoint therapy for the treatment of cold tumors, based on the simultaneous activation of antitumoral innate and adaptive immunity

2021-08-13 | GSE165612 | GEO

M. tuberculosis reprograms HSCs to limit myelopoiesis and impair trained immunity via a type I IFN/iron axis [EG_SERIES_3]

Project description:A greater understanding of hematopoietic stem cell (HSC) regulation is required for dissecting protective versus detrimental immunity to pathogens that cause chronic infections such as Mycobacterium tuberculosis (Mtb). We have shown that systemic administration of BCG or b-glucan reprograms HSCs in the BM via a type II interferon (IFN-II) or IL1 response, respectively, that confers protective trained immunity against Mtb. Yet, whether BCG/β-Glucan is unique in its ability to induce this protection remains unknown. Herein, we demonstrate that unlike BCG or b-glucan, Mtb reprograms HSCs via IFN-I response that suppresses myelopoiesis and impairs protective trained immunity to Mtb. Mechanistically, IFN-I response dysregulates iron metabolism, depolarizes mitochondrial membrane potential, and induces cell death in myeloid progenitors. Finally, activation of IFN-I/iron axis in myeloid progenitors generates a detrimental trained immunity to Mtb infection. These results identify an unanticipated immune evasion strategy of Mtb in the bone marrow that controls the magnitude and anti-microbial capacity of innate immunity to infection

2020-08-13 | GSE156136 | GEO

M. tuberculosis reprograms HSCs to limit myelopoiesis and impair trained immunity via a type I IFN/iron axis [AERO_SERIES_2]

2020-08-13 | GSE156135 | GEO

M. tuberculosis reprograms HSCs to limit myelopoiesis and impair trained immunity via a type I IFN/iron axis [Bulk_SERIES_1]

2020-08-13 | GSE156134 | GEO