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

Elife. 2020 Mar 5:9: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.

Keywords: EsxA; Mycobacterium tuberculosis; Type VII secretion system; human; immunology; infectious disease; inflammation; microbiology; microfold cell; mouse; mucosal immunology; scavenger receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoids / cytology
  • Adenoids / microbiology
  • Animals
  • Cell Line, Tumor
  • Gene Expression Regulation
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis / classification
  • Mycobacterium tuberculosis / physiology*
  • Nose
  • Scavenger Receptors, Class B / physiology*
  • Type VII Secretion Systems / physiology

Substances

  • Scavenger Receptors, Class B
  • Type VII Secretion Systems