Identification of scavenger receptor B1 as the airway microfold cell receptor for Mycobacterium tuberculosis
- University of Texas Southwestern Medical School, United States
- University of Texas Southwestern Medical Center, United States
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.
Article and author information
Author details
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
- Christina L Stallings, Washington University School of Medicine, United States
Publication history
- Received: October 8, 2019
- Accepted: March 4, 2020
- Accepted Manuscript published: March 5, 2020 (version 1)
- Version of Record published: March 11, 2020 (version 2)
- 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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