Mouse gut metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA498533 | ENA |
REPOSITORIES: ENA
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Project description:Compartmentalized gut lymph node drainage dictates adaptive immune responses
| PRJNA498502 | ENA
Project description:Purpose: The intestine's main function is to digest and absorb dietary nutrients, with help from the absorptive epithelium and underlying vasculature and lymphatic system, as well as the microbiome. The intestine also houses the largest immune cell population in the body, tasked with providing resistance to toxins and invading pathogens while maintaining tolerance to dietary and microbial antigens, either by local action or lymphatic trafficking to the gut-draining lymph nodes (gLNs) to mount adaptive responses. While previous studies revealed the drainage map to various gLNs along the murine gut, and described immunological differences between gLNs, the underlying cellular components and the functional consequences of gut segment-specific drainage have not been systematically addressed. We sought to understand how compartmentalized lymphatic drainage of the intestinal milieu contributes to immune responses towards luminal antigens. Results: Here we report that gLNs are immunologically unique according to the functional gut segment they drain. Stromal and dendritic cell gene signatures, as well as adaptive T cell polarization against the same luminal antigen, differed between gLNs along the intestine, the proximal small intestine–draining gLNs preferentially giving rise to tolerogenic and the distal gLNs to pro-inflammatory T cell responses. This compartmentalized dichotomy could be perturbed by duodenal infection, surgical removal of select distal gLNs, dysbiosis, or ectopic antigen delivery, impacting both lymphoid organ and tissue immune responses. Conclusions: Our findings reveal that the conflict between tolerogenic and inflammatory adaptive responses is in part resolved by discrete gLN drainage, and encourage gut segment-specific antigen targeting for therapeutic immune modulation.
2019-04-10 | GSE121811 | GEO
Project description:Current immunosuppressants effectively suppress adaptive and innate immune responses, but their broad, antigen-non-specific effects often result in significant complications. Here we investigated understudied immunosuppressant effects of four major immunosuppressant classes including tacrolimus, prednisone, mycophenolate mofetil (MMF), and Fingolimod (FTY), on the gut microbiome, metabolic pathways, lymphoid architecture and lymphocyte trafficking. Despite their distinct mechanisms of action, all drugs induced progressive alterations from moderate early changes to substantial alterations in the gut microbiome composition and metabolic pathways with prolonged treatment, converging to a shared dysbiotic state. This was accompanied by significant metabolic alterations and distinct phases of intestinal transcriptional responses. Time-dependent changes in lymph node (LN) reorganization and cellular composition were also observed, showing compartmentalized immune regulation in mesenteric and peripheral lymphoid tissues. Together, these findings highlight the underappreciated complexity and temporal dynamics of immunosuppressant effect, linking drug-induced changes in gut microbiome and compartmentalized immune regulation in lymphoid tissues. Notably, MMF and FTY demonstrated most robust immunomodulatory properties, and were able to suppress alloantigen-induced inflammation through mediating regulatory T cells and LN remodeling. Understanding these relationships provides new opportunities for refining immunosuppressive strategies to mitigate treatment-related complications in transplant patients, ultimately improving long-term organ transplant outcomes.
2025-06-24 | GSE288074 | GEO
Project description:Lymph nodes are secondary lymphoid tissues that play a critical role in filtering the lymph and supporting adaptive immune responses. Surgical resection of LNs, radiation therapy or infections may damage lymphatic vasculature and compromised immune functions. Here, we describe the generation of functional synthetic lympho-organoids (LOs) using LN stromal progenitors and decellularized extra cellular matrix-based scaffolds. We show that upon transplantation at the site of resected LNs, LOs become integrated into the endogenous lymphatic vasculature and efficiently restore lymphatic drainage and perfusion. Upon immunization, LOs support the activation of antigen-specific immune responses, thus acquiring properties of native lymphoid tissues. These findings provide the first proof-of-concept for the development of synthetic lympho-organoids suitable to restore lymphatic and immune cell functions.
2019-11-12 | PXD013250 | Pride
Project description:The non-leukocytic stromal cells of lymph nodes critically regulate immune responsiveness. However, the effects of different SARS-CoV-2 vaccines on stromal cell biology are unknown. We used single-cell transcriptomics to study early responses of stromal cells in draining lymph nodes after immunizing mice with clinically used COVID-19 vaccines, namely Spikevax®, Comirnaty®, Vaxzevria® and Nuvaxovid™. We found that vaccinations lead to robust transcriptomic changes, including vaccine-selective ones, in the different lymph node stromal cell populations priming the lymph node for the upcoming adaptive immune response.
2025-08-15 | GSE300959 | GEO
Project description:Adaptive immune responses are intensely energy-dependent and rely on a local source of fuel-producing molecules which have been proposed to be derived from fat pads in which mammalian lymph nodes are embedded. However, the trigger for their release has not been identified. Here we demonstrate that cutaneous inflammation is directly correlated with rapid atrophy of perinodal fat pads and increase in embedded lymph node size. We further demonstrate that the fat pad atrophy is associated with influx of a CCR2-independent, lipid metabolising, macrophage population and that macrophage depletion ameliorates fat pad atrophy, and lymph node expansion, downstream of inflamed sites. Our data therefore identify peripheral inflammation as an antigen-independent trigger of downstream fat pad and lymph node remodelling and contributes to the release of essential nutrients to drive the energetic requirements of the adaptive immune response.
2026-06-08 | GSE317411 | GEO
Project description:Vaccination triggers coordinated immune responses that begin at the injection site and propagate to draining lymph nodes, yet spatially resolved maps linking these events remain limited. Here, we applied high-plex spatial transcriptomics to profile early responses to an adjuvanted recombinant haemagglutinin (rHA) protein vaccine. In mice, early innate activation was observed in non-follicular lymph node regions at Day 1, transitioning to adaptive, germinal centre–associated responses within follicles by Day 7. At the injection site, stromal and muscle cells exhibited strong chemokine and interferon responses, spatially localised to fibroblast-rich regions. These tissue-level dynamics were accompanied by transient systemic cytokine responses and increased antigen-specific IgG. Together, this study links spatially organised local inflammation with lymph node architecture to define early vaccine-induced immune responses.
2026-04-16 | GSE328253 | GEO
Project description:Vaccination triggers coordinated immune responses that begin at the injection site and propagate to draining lymph nodes, yet spatially resolved maps linking these events remain limited. Here, we applied high-plex spatial transcriptomics to profile early responses to an adjuvanted recombinant haemagglutinin (rHA) protein vaccine. In mice, early innate activation was observed in non-follicular lymph node regions at Day 1, transitioning to adaptive, germinal centre–associated responses within follicles by Day 7. At the injection site, stromal and muscle cells exhibited strong chemokine and interferon responses, spatially localised to fibroblast-rich regions. These tissue-level dynamics were accompanied by transient systemic cytokine responses and increased antigen-specific IgG. Together, this study links spatially organised local inflammation with lymph node architecture to define early vaccine-induced immune responses.
2026-06-25 | GSE336618 | GEO
Project description:Despite the success of currently authorized vaccines for the reduction of severe COVID-19 disease risk, rapidly emerging viral variants continue to drive pandemic waves of infection, resulting in numerous global public health challenges. Progress will depend on future advances in prophylactic vaccine activity, including advancement of candidates capable of generating more potent induction of cross-reactive T cells and durable cross-reactive antibody responses. Here we evaluated an Amphiphile (AMP) adjuvant, AMP-CpG, admixed with SARS-CoV-2 Spike receptor binding domain (RBD) immunogen, as a lymph node-targeted protein subunit vaccine (ELI-005) in mice and non-human primates (NHPs). AMP-mediated targeting of CpG DNA to draining lymph nodes resulted in comprehensive local immune activation characterized by extensive transcriptional reprogramming, inflammatory proteomic milieu, and activation of innate immune cells as key orchestrators of antigen-directed adaptive immunity. Prime-boost immunization with AMP-CpG in mice induced potent and durable T cell responses in multiple anatomical sites critical for prophylactic efficacy and prevention of severe disease. Long-lived memory responses were rapidly expanded upon re-exposure to antigen. In parallel, RBD-specific antibodies were long-lived, and exhibited cross-reactive recognition of variant RBD. AMP-CpG-adjuvanted prime-boost immunization in NHPs was safe and well tolerated, while promoting multi-cytokine-producing circulating T cell responses cross-reactive across variants of concern (VOC). Expansion of RBD-specific germinal center (GC) B cells in lymph nodes correlated to rapid seroconversion with variant-specific neutralizing antibody responses exceeding those measured in convalescent human plasma. These results demonstrate the promise of lymph-node adjuvant-targeting to coordinate innate immunity and generate robust adaptive responses critical for vaccine efficacy.
2022-11-02 | GSE214555 | GEO
Project description:Fibroblastic reticular cells (FRC) shape the organization of secondary lymphoid organs and actively promote the induction of immune responses by coordinating the interaction of innate and adaptive immune cells. However, the mechanisms underlying FRC functions during viral infections have remained largely unexplored. In the study, we combined FRC-specific genetic ablation of the type 1 IFN-alpha receptor (IFNAR) with high-dimensional transcriptomics analyses to elaborate the phenotypical alterations and functional consequences of impaired innate immunological sensing in FRC during lymph node-restricted viral infection
2020-09-01 | E-MTAB-8906 | biostudies-arrayexpress