
CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection

Order Assays
Joshua D. Bromley, Sharie Keanne C. Ganchua, Sarah K. Nyquist, Pauline Maiello, Michael Chao, H. Jacob Borish, Mark Rodgers, Jaime Tomko, Kara Kracinovsky, Douaa Mugahid, Son Nguyen, Dennis Wang, Jacob M. Rosenberg, Edwin C. Klein, Hannah P. Gideon, Roisin Floyd-O’Sullivan, Bonnie Berger, Charles A Scanga, Philana Ling Lin, Sarah M. Fortune, Alex K. Shalek, JoAnne L. Flynn
Link to Paper: https://www.cell.com/immunity/fulltext/S1074-7613(24)00375-3
Immunological priming – either in the context of prior infection or vaccination – elicits protective responses against subsequent Mycobacterium tuberculosis (Mtb) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Here, using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrate that prior Mtb infection elicits a long-lasting protective response against subsequent Mtb exposure and that the depletion of CD4+ T cells prior to Mtb rechallenge significantly abrogates this protection. Leveraging microbiologic, PET-CT, flow cytometric, and single-cell RNA-seq data from primary infection, reinfection, and reinfection-CD4+ T cell depleted granulomas, we identify differential cellular and microbial features of control. The data collectively demonstrate that the presence of CD4+ T cells in the setting of reinfection results in a reduced inflammatory lung milieu characterized by reprogrammed CD8+ T cell activity, reduced neutrophilia, and blunted type-1 immune signaling among myeloid cells, mitigating Mtb disease severity. These results open avenues for developing vaccines and therapeutics that not only target CD4+ and CD8+ T cells, but also modulate innate immune cells to limit Mtb disease.
Export PNG

Views: 318
Created: 7th Dec 2023 at 20:40
Last updated: 9th Dec 2024 at 19:41

This item has not yet been tagged.
Related items
- People (1)
- Programmes (1)
- Projects (1)
- Investigations (1)
- Assays (11)
- Data files (20)
- SOPs (11)
- Samples (3304)
Projects: Hi-IMPAcTB, MIT SRP, MetNet, Endometriosis, Cancer Systems Biology Consortium (CSBC)
Institutions: Massachusetts Institute of Technology
About
This project houses all the publicly available datasets generated by the Hi-IMPAcTB consortium over the course of its 7+ years.
What is Hi-IMPAcTB?
Hi-IMPAcTB is an ambitious endeavor bringing together a team of international, interdisciplinary researchers to improve our understanding of host-pathogen interactions in the context of tuberculosis (TB). Funded by a multi-center contract from the NIH, the long-term goal of the consortium is to enable principled vaccine design by improving ...
Programme: Metastasis Network
Public web page: https://grantome.com/grant/NIH/75N93019C00071-0-9999-1
Organisms: Mus musculus, Homo sapiens, Macaca fascicularis, Macaca mulatta
Submitter: Dikshant Pradhan
Studies: Age and sex influence antibody profiles associated with tuberculosis pro..., CD4+ T cells re-wire granuloma cellularity and regulatory networks to pr..., CD8+ lymphocytes are critical for early control of tuberculosis in macaques, Fc-FcγR interactions shift alveolar macrophage metabolism to promote Myc..., Fc-engineered antibodies leverage neutrophils to drive control of Mycoba..., High-dose intravenous BCG vaccination induces enhanced immune signaling ..., Humoral correlates of protection against Mycobacterium tuberculosis foll..., Immune cells in bronchoalveolar lavage fluid of Ugandan adults who resis..., Intravenous BCG-mediated protection against tuberculosis requires CD4+ T..., Multi-modal data integration using Markov Field graphical networks predi..., Multimodal profiling of lung granulomas in macaques reveals cellular cor..., Robust IgM responses following intravenous vaccination with Bacille Calm..., Specific CD4+ T cell phenotypes associate with bacterial control in peop..., Systems-level computational translation of mouse and human transcriptomi...
Assays: All Metadata, All Metadata, All Metadata, All Metadata, All Metadata, All Metadata, All Metadata, Anti-Microbial Assay – Metadata, Antibody Challenge - Metadata, Antibody Titer - Data Linked, Antibody Titer Analysis - Data Linked, Antibody-Dependent Cellular Phagocytosis - Data Linked, Antibody-Dependent Cellular Phagocytosis - Data Linked, Antibody-Dependent Cellular Phagocytosis Analysis - Data Linked, Antibody-Dependent NK Cell Activation - Data Linked, Antibody-Dependent NK Cell Activation Analysis - Data Linked, Antibody-Dependent Neutrophil Phagocytosis - Data Linked, Antibody-Dependent Neutrophil Phagocytosis - Data Linked, Antibody-Dependent Neutrophil Phagocytosis Analysis - Data Linked, Antibody-dependent Cellular Phagocytosis - Data Linked, Antibody-dependent Complement Deposition - Data Linked, Antibody-dependent NK Cell Activation - Data Linked, Antibody-dependent Neutrophil Phagocytosis - Data Linked, Bacterial Challenge - Metadata, Bacterial Extraction - Metadata, Bacterial Extraction - Metadata, Bacterial Extraction - Metadata, Bacterial Survivability Restriction Assay - Data Linked, Bacterial Survivability Restriction Assay: Validation Data - Data Attached, Cell Extraction: Validation Data - Metadata, DNA Extraction - Metadata, Digitally Barcoded Mtb Matrix Analysis - Data Attached, Digitally Barcoded Mtb Matrix Analysis - Data Attached, Digitally Barcoded Mtb Matrix Analysis - Data Attached, ELISA - Data Linked, FC Receptor Binding - Data Linked, FC Receptor Binding Analysis - Data Linked, FC Receptor Binding Assay - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry Analysis - Data Attached, Flow Cytometry Analysis - Data Linked, Flow Cytometry Analysis - Data Linked, Flow Cytometry Analysis - Data Linked, Flow Cytometry Analysis - Data Linked, Flow Cytometry Processing – Data Attached, Flow Cytometry – Data Linked, Functional Assay – Metadata, Gene Expression Analysis: Training Data - Data Linked, Gene Expression Analysis: Validation Data - Data Linked, Glycosylation Assay - Data Linked, Histology - Data Linked, Immunohistochemistry - Data Linked, Immunohistochemistry – Data Linked, Library Creation - Metadata, Library Creation – Metadata, Library Prep - Metadata, Library Prep - Metadata, Library Prep - Metadata, Library Prep: Training Data - Metadata, Library Prep: Validation Data - Metadata, Linear Mixed Model - Data Linked, Luminex - Data Linked, Luminex Assay – Metadata, Luminex Data Processing – Data Attached, Model Validation, NHP Necropsy – Metadata, NHP Tissue Collection – Metadata, PCR: Validation Data - Data Attached, PET-CT Scan - Data Linked, PET-CT Scan - Data Linked, PET-CT Scan Analysis – Data Linked, PET-CT Scan – Data Linked, PET/CT Scan - Data Linked, PET/CT Scan - Data Linked, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit – Metadata, Patient Visit – Metadata, RNA Extraction: Validation Data - Metadata, Short Read Sequencing - Data Linked, Short Read Sequencing - Data Linked, Short Read Sequencing - Data Linked, Short Read Sequencing - Data Linked, Short Read Sequencing: Training Data - Data Linked, Short Read Sequencing: Validation Data - Data Linked, Single Cell Clustering Analysis - Data Linked, Single Cell Clustering Analysis – Data Linked, Single Cell Expression Analysis - Data Linked, Single Cell Expression Analysis - Data Linked, Single Cell Expression Analysis - Data Linked, Single Cell Expression Analysis - Data Linked, Single Cell Expression Matrix Analysis – Data Linked, Single Cell Sequencing Analysis – Data Linked, Single Cell Sequencing – Data Linked, Single Cell Sequencing – Data Linked, Tissue Collection - Metadata, Tissue Collection - Metadata, Tissue Collection - Metadata, Tissue Collection - Metadata, Tissue Collection - Metadata, Tissue Collection - Metadata, Tissue Collection - Metadata, Tissue Collection - Metadata, Tissue Collection - Metadata, Tissue Collection: Training Data - Metadata, Tissue Extraction - Metadata, Tissue Extraction – Metadata, Titer Assay - Data Linked, Titer Assay - Data Linked, Titer Assay Analysis - Data Linked, TransCompR Cross Species Modeling - Data Linked
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Organisms: No organisms
SOPs: P.FLY-240716_V1_CD4_NHPs.docx, P.FLY-240716_V1_CD4_NX_Procedure.docx
Data files: CD4-Depletion-Reinfection Study Design Graphic, samples-publishJB_CD4_AB.xlsx, samples-publishJB_CD4_BAC.xlsx, samples-publishJB_CD4_NHP.xlsx, samples-publishJB_CD4_PAV.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Organisms: No organisms
SOPs: P.FLY-210708-V1_Hannah's-GentleMacs-Protocol-as..., P.FLY-240716_V1_CD4_CFU_LibraryIdentification.docx, P.FLY-240716_V1_CD4_NX_Procedure.docx
Data files: samples-publishJB_CD4_PAV.xlsx, samples-publishJB_CD4_TIS.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Organisms: No organisms
SOPs: P.FOR-231011_Bacterial Extraction
Data files: samples-publishJB_CD4_BAC.xlsx, samples-publishJB_CD4_TIS.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Organisms: No organisms
SOPs: P.FOR-230503-V1_Barcoding_Amplicon_Feb2023, P.SHA-220819-V1_SeqWellHughes.et.al.Master.Prot...
Data files: samples-publishJB_CD4_BAC.xlsx, samples-publishJB_CD4_DNA.xlsx, samples-publishJB_CD4_DNA.xlsx, samples-publishJB_CD4_TIS.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Organisms: No organisms
SOPs: P.FLY-240716_V1_CD4_scRNAseq.docx, P.FOR-230503-V1_Barcoding_Amplicon_Feb2023
Data files: samples-publishJB_CD4_D.SEQ.xlsx, samples-publishJB_CD4_D.SEQ.xlsx, samples-publishJB_CD4_DNA.xlsx, samples-publishJB_CD4_DNA.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Organisms: No organisms
SOPs: P.FLY-240716_V1_CD4_scRNAseq.docx, P.SHA-220912-V1_Drop-seq_Alignment_Cookbook.pdf
Data files: samples-publishJB_CD4_A.SCXP.xlsx, samples-publishJB_CD4_D.SEQ.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Organisms: No organisms
SOPs: No SOPs
Data files: aCD4_cleaned_data_stats_circos, samples-publishJB_CD4_A.DBMM.xlsx, samples-publishJB_CD4_D.SEQ.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Organisms: No organisms
SOPs: P.FLY-240716_V1_CD4_ICS_FlowCytometry.docx
Data files: samples-publishJB_CD4_AB.xlsx, samples-publishJB_CD4_ABP.xlsx, samples-publishJB_CD4_D.FLOW.xlsx, samples-publishJB_CD4_TIS.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Organisms: No organisms
SOPs: No SOPs
Data files: samples-publishJB_CD4_A.FLOW.xlsx, samples-publishJB_CD4_D.FLOW.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Organisms: No organisms
SOPs: P.FLY-230523-V1_PET_CT_Imaging
Data files: samples-publishJB_CD4_D.IMG.xlsx, samples-publishJB_CD4_PAV.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: IMPAcTB
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: All Metadata
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Flow Cytometry - Data Linked, Flow Cytometry Analysis - Data Linked
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Flow Cytometry - Data Linked
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Flow Cytometry - Data Linked
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Short Read Sequencing - Data Linked, Single Cell Expression Analysis - Data Linked
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Digitally Barcoded Mtb Matrix Analysis - Data A..., Short Read Sequencing - Data Linked
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Library Prep - Metadata, Short Read Sequencing - Data Linked
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Library Prep - Metadata, Short Read Sequencing - Data Linked
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Bacterial Extraction - Metadata, Library Prep - Metadata
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: PET-CT Scan - Data Linked
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Patient Visit - Metadata
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Patient Visit - Metadata
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: PET-CT Scan - Data Linked, Patient Visit - Metadata, Tissue Collection - Metadata
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: IMPAcTB
Studies: CD4+ T cells re-wire granuloma cellularity and ...
Assays: Patient Visit - Metadata