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    Home > Active Ingredient News > Immunology News > Nature Immunology Mapping the immune regulatory network of human Mycobacterium tuberculosis granulomas

    Nature Immunology Mapping the immune regulatory network of human Mycobacterium tuberculosis granulomas

    • Last Update: 2022-03-09
    • Source: Internet
    • Author: User
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    Written | Edited by Xue Yue | Xi Mycobacterium tuberculosis Mtb infection kills 1.
    5 million people every year
    .

    However, the response of the human immune system to Mtb has not been fully elucidated, hindering the development of host-directed therapies
    .

    Mycobacterium tuberculosis is inhaled into the lungs and engulfed by macrophages, triggering an immune response and forming granulomas
    .

    Granuloma is a dynamic spatial structure composed of macrophages, granulocytes, lymphocytes and fibroblasts
    .

    Granulomas isolate infection sites from uninvolved lung tissue on the one hand to limit transmission, and on the other hand, tolerance pathways upregulated at granuloma sites limit Mycobacterium tuberculosis clearance
    .

    The composition of granulomas is highly variable
    .

    Even in a single individual, infection can lead to granulomas with different histological features
    .

    Each granuloma changes independently over time
    .

    In nonhuman primate infection models, there are more than ten granulomas per individual individual, and each granuloma varies widely in inflammatory characteristics, size, and bacterial ecology
    .

    Recently, Michael Angelo's team from Stanford University published an article entitled The immunoregulatory landscape of human tuberculosis granulomas in Nature Immunology, mapping the immune regulatory network of human tuberculosis granulomas
    .

    The authors first examined immune cell composition in human binding granulomas
    .

    Tissue samples were obtained from paraffin-embedded samples of treated patients
    .

    Paraffin-embedded samples were obtained from excised tissue from advanced tuberculosis in South Africa; lung tissue from fatal tuberculosis and autopsy of patients in the United States
    .

    Sample collection sites include the lungs, pleural cavity, lymph nodes, vertebrae, and endometrium
    .

    The authors performed MIBI-TOF imaging of the samples for antibodies including markers of immune and non-immune cell lineages and markers of immune activity, including lymphocytes, macrophages, granulocytes, and epithelial cells
    .

    After labeling, in order to extract information about individual cells, the authors performed phenotype analysis on each image using FlowSOM
    .

    The results showed that T cells and myeloid cells predominated in granulomas
    .

    Through different markers, myeloid cells can be differentiated into macrophages, DCs and monocytes
    .

    The authors also calculated that γδT cells accounted for 0.
    1%, CD209+DC 0.
    2%, and Treg 1%
    .

    This suggests that the method can identify cell populations that are less abundant
    .

    Consistent with previous reports, active granulomas showed increased blood vessels and endothelial cells accounted for 3.
    7%
    .

    The proportions of fibroblasts and epithelial cells vary by lesion
    .

    The authors classified 94% of the detected, approximately 39,709 single cells into 19 cell populations
    .

    The authors carefully analyzed the relationship between 19 cell populations and TB disease status and found that a comprehensive cell census can reveal different types of granulomas, mainly determined by the frequency of immune cells
    .

    The authors next analyzed the association of spatial structure and function in granulomas
    .

    The authors performed a spatial enrichment analysis to quantify how often the two markers appeared together
    .

    Spatial analysis revealed a feature that could not be identified at the level of global analysis, namely the presence of spatially cooperating cellular responses in granulomas
    .

    For example, some granulomas exhibit a fibrotic wound-healing response, and in these sites CD163+M2-like macrophages are spatially distributed close to fibroblasts
    .

    By evaluating immune activity markers such as PD-L1 IDO1, the authors found that myeloid cells in granulomas play an immunosuppressive role, while the activation of lymphocytes distributed in granulomas is sporadic
    .

    Finally, the authors analyzed the peripheral blood transcriptional profiles of healthy individuals and tuberculosis patients to analyze immune activation in peripheral blood
    .

    The authors found that the immune status of granulomas and peripheral blood were synchronized and correlated with tuberculosis infection
    .

    In this study, we performed analysis of cellular composition, mapping of spatial distribution, and exploration of immune regulatory pathways in granulomas following Mycobacterium tuberculosis infection, and established a link between granulomas and peripheral immune responses, for the development of host-oriented immune responses.
    Therapy provides the basics of immunology
    .

    Original link: https://doi.
    org/10.
    1038/s41590-021-01121-x Publisher: 11th reprint notice [Original article] BioArt original article, welcome to forward and share personally, reprint is prohibited without permission, all published articles The copyright of the work is owned by BioArt
    .

    BioArt reserves all legal rights and violators will be held accountable
    .

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