1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Identification of scavenger receptor B1 as the airway microfold cell receptor for Mycobacterium tuberculosis

  1. Haaris S Khan
  2. Vidhya R Nair
  3. Cody R Ruhl
  4. Samuel Alvarez-Arguedas
  5. Jorge L Galvan Rendiz
  6. Luis H Franco
  7. Linzhang Huang
  8. Philip W Shaul
  9. Jiwoong Kim
  10. Yang Xie
  11. Ron B Mitchell
  12. Michael U Shiloh  Is a corresponding author
  1. University of Texas Southwestern Medical School, United States
  2. University of Texas Southwestern Medical Center, United States
Research Article
  • Cited 5
  • Views 1,486
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Cite this article as: eLife 2020;9:e52551 doi: 10.7554/eLife.52551

Abstract

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.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Whole genome sequencing data have been deposited at NCBI Sequence Read Archive, Accession #PRJNA605439.

The following data sets were generated

Article and author information

Author details

  1. Haaris S Khan

    Internal Medicine, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Vidhya R Nair

    Internal Medicine and Microbiology, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Cody R Ruhl

    Internal Medicine, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Samuel Alvarez-Arguedas

    Internal Medicine, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jorge L Galvan Rendiz

    Internal Medicine, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Luis H Franco

    Internal Medicine and Microbiology, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Linzhang Huang

    Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Philip W Shaul

    Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Jiwoong Kim

    Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Yang Xie

    Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Ron B Mitchell

    Otolaryngology, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Michael U Shiloh

    Internal Medicine and Microbiology, University of Texas Southwestern Medical School, Dallas, United States
    For correspondence
    michael.shiloh@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4329-2253

Funding

National Institute of Allergy and Infectious Diseases (AI125939)

  • Michael U Shiloh

National Institute of Allergy and Infectious Diseases (AI142784)

  • Michael U Shiloh

National Institute of Allergy and Infectious Diseases (5T32AI005284)

  • Haaris S Khan

National Heart, Lung, and Blood Institute (HK131597)

  • Philip W Shaul

Burroughs Wellcome Fund (1017894)

  • Michael U Shiloh

Welch Foundation (I-1964-20180324)

  • Michael U Shiloh

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee at the University of Texas Southwestern (protocol 2017-101836) and followed the eighth edition of the Guide for the Care and Use of Laboratory Animals. The University of Texas Southwestern is accredited by the American Association for Accreditation of Laboratory Animal Care (AAALAC).

Human subjects: Human adenoids were obtained from children undergoing elective adenoidectomy for sleep apnea after informed consent was obtained from parents or guardians. This study was reviewed by the University of Texas Southwestern Institutional Review Board (protocol STU 062016-087).

Reviewing Editor

  1. Christina L Stallings, Washington University School of Medicine, United States

Publication history

  1. Received: October 8, 2019
  2. Accepted: March 4, 2020
  3. Accepted Manuscript published: March 5, 2020 (version 1)
  4. Version of Record published: March 11, 2020 (version 2)
  5. Version of Record updated: March 11, 2020 (version 3)

Copyright

© 2020, Khan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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