Immune cell interactions in tuberculosis

Flynn, JoAnne L.; Chan, John

doi:10.1016/j.cell.2022.10.025

Cited by 64 publications

(40 citation statements)

References 220 publications

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“…Our finding of a higher magnitude of IL17-than IFNγ-producing CD4 + T cells in HIV-ART upon Mtb300 stimulation is contrary to the impression that IFNg production is the dominant response to Mtb infection [41]. This may have implications for TB diagnosis since current tests for detection of responses to Mtb antigens rely on IFNγ production, whose sensitivity is variable and is impacted by HIV infection [42].…”

contrasting

confidence: 73%

High-parameter phenotypic characterization reveals a subset of human Th17 cells that preferentially produce IL17 againstM. tuberculosisantigen

Ogongo

Tran

Marzan

et al. 2023

Preprint

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Background: Interleukin 17 producing CD4 T cells contribute to control of Mycobacterium tuberculosis (Mtb) infection in humans; whether infection with Human Immunodeficiency Virus (HIV) disproportionately affects distinct Th17 cell subsets that respond to Mtb are incompletely defined. Methods: We performed high-definition characterization of circulating Mtb-specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity in plasma by LC/MS and tested the hypothesis that tryptophan catabolism influences Th17 cell differentiation in this context. Results: We identified two categories of Th17 cells: TH17 (CD4+Vα7.2-CD161+CD26+) and T17 (CD4+Vα7.2-CCR6+CXCR3-) cells that were disproportionately reduced in LTBI with HIV-ART, yet Mtb-responsive IL17-producing CD4 T cells were preserved; we found that IL17-producing CD4 T cells dominate the response to Mtb antigen but not CMV antigen or staphylococcal enterotoxin B (SEB); and tryptophan catabolism negatively correlates with TH17 and T1T17 but not T17 cell frequencies. Conclusions: We found differential effects of ART-suppressed HIV on distinct categories of Th17 cells, that IL17-producing CD4 T cells dominate responses to Mtb but not CMV antigen or SEB, and that kynurenine pathway activity is associated with selective decreases of circulating Th17 cells that may contribute to tuberculosis immunity.

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contrasting

confidence: 73%

High-parameter phenotypic characterization reveals a subset of human Th17 cells that preferentially produce IL17 againstM. tuberculosisantigen

Ogongo

Tran

Marzan

et al. 2023

Preprint

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“…Long-recognized hallmarks of tuberculosis pathology are granulomas in the lung which form around the sites of initial infection by Mycobacterium tuberculosis (Mtb). They form as tissue-resident macrophages phagocytize the pathogen while simultaneously recruiting other immune cells including dendritic cells, monocytes, neutrophils, NK cells, and T and B cells to the site of infection via the release of chemokines and cytokines (1)(2)(3). Granulomas minimize damage to larger lung tissue by locally restricting both bacterial proliferation and inflammatory immune responses (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

“…Although signatures of the immune response to Mtb are present in the peripheral blood as memory T cells (4, 5) and as transcriptomic markers (6), the most intimate and long-term contact between Mtb and the host immune system occurs within the confines of the granuloma (3). It is therefore more informative to study interactions between the pathogen and the immune system through studies of the functional architecture of granulomas.…”

Section: Introductionmentioning

confidence: 99%

Imaging Architecture of Granulomas Induced byMycobacterium tuberculosisInfections with Single-Molecule FISH

Kumar

Kolloli

Subbian

et al. 2023

Preprint

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Granulomas are an important hallmark of Mycobacterium tuberculosis (Mtb) infection. They are organized and dynamic structures created by an assembly of immune cells around the sites of infection in the lungs to locally restrict the bacterial growth and the host's inflammatory responses. The cellular architecture of granulomas is traditionally studied by immunofluorescence labeling of phenotypic surface markers. However, very few antibodies are available for model animals used in tuberculosis research, such as non-human primates and rabbits; secreted immunological markers such as cytokines cannot be imaged in situ using antibodies; and traditional phenotypic surface markers do not provide sufficient resolution for the detection of many subtypes and differentiation states of immune cells. Using single-molecule fluorescent in situ hybridization (smFISH) and its derivatives, amplified smFISH (ampFISH) and iterative smFISH, we developed a platform for imaging mRNAs encoding immune markers in rabbit and macaque tuberculosis granulomas. Multiplexed imaging for several mRNA and protein markers was followed by quantitative measurement of expression of these markers in single cells in situ. A quantitative analysis of combinatorial expressions of these markers allowed us to classify the cells into several subtypes and chart their distributions within granulomas. For one mRNA target, HIF-1 alpha, we were able to image its mRNA and protein in the same cells, demonstrating the specificity of probes. This method paves the way for defining granular differentiation states and cell subtypes from transcriptomic data, identifying key mRNA markers for these cell subtypes, and then locating the cells in the spatial context of granulomas.

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“…Usually, sputum smear microscopy is the most extensively used; however, regardless of its high specificity, its low sensitivity restricts its diagnostic value ( 7 ). However, TB cultures take nearly 42 days to detect identifiable growth, thus the long culture period limits its clinical diagnosis ( 8 ). At present, the Xpert MTB/RIF and ultra-version tests detect genetic material from M. tb as sensitively as microbial cultures ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Functions of exosomal non-coding RNAs to the infection with Mycobacterium tuberculosis

Wang

et al. 2023

Front. Immunol.

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Tuberculosis (TB) is a major infectious disease induced by Mycobacterium tuberculosis (M. tb) which causes the world’s dominant fatal bacterial contagious disease. Increasing studies have indicated that exosomes may be a novel option for the diagnosis and treatment of TB. Exosomes are nanovesicles (30-150 nm) containing lipids, proteins and non-coding RNAs (ncRNAs) released from various cells, and can transfer their cargos and communicate between cells. Furthermore, exosomal ncRNAs exhibit diagnosis potential in bacterial infections, including TB. Additionally, differential exosomal ncRNAs regulate the physiological and pathological functions of M. tb-infected cells and act as diagnostic markers for TB. This current review explored the potential biological roles and the diagnostic application prospects of exosomal ncRNAs, and included recent information on their pathogenic and therapeutic functions in TB.

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Immune cell interactions in tuberculosis

Cited by 64 publications

References 220 publications

High-parameter phenotypic characterization reveals a subset of human Th17 cells that preferentially produce IL17 againstM. tuberculosisantigen

High-parameter phenotypic characterization reveals a subset of human Th17 cells that preferentially produce IL17 againstM. tuberculosisantigen

Imaging Architecture of Granulomas Induced byMycobacterium tuberculosisInfections with Single-Molecule FISH

Functions of exosomal non-coding RNAs to the infection with Mycobacterium tuberculosis

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