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

Haaris S. Khan; Vidhya R. Nair; Cody R. Ruhl; Samuel Alvarez-Arguedas; Jorge L.Galvan Rendiz; Luis H. Franco; Linzhang Huang; Philip W. Shaul; Jiwoong Kim; Yang Xie; Ron B. Mitchell; Michael U. Shiloh

doi:10.7554/eLife.52551

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

Haaris S. Khan, Vidhya R. Nair, Cody R. Ruhl, Samuel Alvarez-Arguedas, Jorge L.Galvan Rendiz, Luis H. Franco, Linzhang Huang, Philip W. Shaul, Jiwoong Kim, Yang Xie, Ron B. Mitchell, Michael U. Shiloh

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	English (US)
Article number	e52551
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.52551
State	Published - Mar 2020

ASJC Scopus subject areas

Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

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10.7554/eLife.52551

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@article{708c384be949498288ccb6b32b2128e0,

title = "Identification of scavenger receptor B1 as the airway microfold cell receptor for mycobacterium tuberculosis",

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.",

author = "Khan, {Haaris S.} and Nair, {Vidhya R.} and Ruhl, {Cody R.} and Samuel Alvarez-Arguedas and Rendiz, {Jorge L.Galvan} and Franco, {Luis H.} and Linzhang Huang and Shaul, {Philip W.} and Jiwoong Kim and Yang Xie and Mitchell, {Ron B.} and Shiloh, {Michael U.}",

note = "Funding Information: We thank Beth Levine and members of the Shiloh Lab for constructive feedback on the manuscript. This work is supported by the Burroughs Wellcome Fund 1017894 (MUS), Welch Foundation I-1964– 20180324 (MUS), NIH U01 AI125939-04 (MUS), NIH U19 AI142784-01 (MUS), NIH 5T32AI005284-40 (HSK), and NIH R01 HL131597-03 (PWS). Publisher Copyright: {\textcopyright} Khan et al.",

year = "2020",

month = mar,

doi = "10.7554/eLife.52551",

language = "English (US)",

volume = "9",

journal = "eLife",

issn = "2050-084X",

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T1 - Identification of scavenger receptor B1 as the airway microfold cell receptor for mycobacterium tuberculosis

AU - Khan, Haaris S.

AU - Nair, Vidhya R.

AU - Ruhl, Cody R.

AU - Alvarez-Arguedas, Samuel

AU - Rendiz, Jorge L.Galvan

AU - Franco, Luis H.

AU - Huang, Linzhang

AU - Shaul, Philip W.

AU - Kim, Jiwoong

AU - Xie, Yang

AU - Mitchell, Ron B.

AU - Shiloh, Michael U.

N1 - Funding Information: We thank Beth Levine and members of the Shiloh Lab for constructive feedback on the manuscript. This work is supported by the Burroughs Wellcome Fund 1017894 (MUS), Welch Foundation I-1964– 20180324 (MUS), NIH U01 AI125939-04 (MUS), NIH U19 AI142784-01 (MUS), NIH 5T32AI005284-40 (HSK), and NIH R01 HL131597-03 (PWS). Publisher Copyright: © Khan et al.

PY - 2020/3

Y1 - 2020/3

N2 - 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.

AB - 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.

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

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