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
Affiliations
Haaris S Khan
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
Vidhya R Nair
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
Cody R Ruhl
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
Samuel Alvarez-Arguedas
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
Jorge L Galvan Rendiz
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
Luis H Franco
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
Linzhang Huang
Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, United States
Philip W Shaul
Center for Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, United States
Jiwoong Kim
Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, United States
Yang Xie
Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, United States; Harold C Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, United States; Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, United States
Ron B Mitchell
Department of Otolaryngology, University of Texas Southwestern Medical Center, Dallas, United States
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, United States
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.
