Identification of scavenger receptor B1 as the airway microfold cell receptor for Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) can enter the body through multiple routes, including via specialized transcytotic cells called microfold cells (M cell). However, the mechanistic basis for M cell entry remains undefined. Here, we show that M cell transcytosis depends on the Mtb Type VII secretion machine and its major virulence factor EsxA. We identify scavenger receptor B1 (SR-B1) as an EsxA receptor on airway M cells. SR-B1 is required for Mtb binding to and translocation across M cells in mouse and human tissue. Together, our data demonstrate a previously undescribed role for Mtb EsxA in mucosal invasion and identify SR-B1 as the airway M cell receptor for Mtb.
Source: eLife - Category: Biomedical Science Tags: Immunology and Inflammation Microbiology and Infectious Disease Source Type: research

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As important virulence factors of Mycobacterium tuberculosis, EsxA and EsxB not only play a role in phagosome rupture and M. tuberculosis cytosolic translocation but also function as modulators of host immune responses by modulating numerous microRNAs (miRNAs). Recently, we have found that mycobacterial infection downregulated miR-148a-3p (now termed miR-148) in macrophages in an ESX-1-dependent manner. The upregulation of miR-148 reduced mycobacterial intracellular survival. Here, we investigated miR-147-3p (now termed miR-147), a negative regulator of inflammatory cytokines (e.g., interleukin-6 [IL-6] and IL-10), in myco...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Molecular Pathogenesis Source Type: research
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Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: Biological Sciences Source Type: research
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Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Molecular Bases of Disease Source Type: research
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Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research
Authors: Wang S, Zhou K, Yang X, Zhang B, Zhao Y, Xiao Y, Yang X, Yang H, Guddat LW, Li J, Rao Z Abstract Type VII secretion systems (T7SSs) are found in many disease related bacteria including Mycobacterium tuberculosis (Mtb). ESX-1 [early secreted antigen 6 kilodaltons (ESAT-6) system 1] is one of the five subtypes (ESX-1~5) of T7SSs in Mtb, where it delivers virulence factors into host macrophages during infection. However, little is known about the molecular details as to how this occurs. Here, we provide high-resolution crystal structures of the C-terminal ATPase3 domains of EccC subunits from four different M...
Source: Protein and Cell - Category: Cytology Tags: Protein Cell Source Type: research
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Source: Progress in Biophysics and Molecular Biology - Category: Molecular Biology Source Type: research
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Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Tuberculosis Source Type: research
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Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Microbiology Source Type: research
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Source: Inflammation - Category: Allergy & Immunology Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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