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.

Microbiome-immune interactions in tuberculosis

“…This process has been reported to be facilitated by interactions between the M . tuberculosis virulence factor EsxA and scavenger receptor B1 on M cells in the airway epithelium [ 91 ]. With microbiota composition implicated in M cell density and functionality in the gut [ 92 ], microbiota contributions to airway M cell functions remain to be elucidated, including implications for M .…”

Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis

“…Overexpression of Scavenger receptor B1 (SR-B1) in immortal cells was associated with increased BCG and Mtb binding to the cells, but the corresponding KO in murine macrophages had no effect on BCG binding (110). SR-B1 was essential for EsxA-mediated transcytosis of Mtb across M cells (111). A related SR-B family member, CD36, was identified with a Drosophila RNAi screen to be essential for uptake of M. fortuitum (112).…”

A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium–Host Interaction

“…The beads coated with the purified EsxA efficiently translocate across the M cell layer, suggesting that EsxA plays a role in mediating Mtb entry into the M cells. Subsequent co-immunoprecipitation identifies that EsxA interacts with scavenger B-1 in M cells, indicating that scavenger B-1 may function as a surface receptor for EsxA to mediate Mtb invasion in cells and animal models [ 60 ].…”

“…Interestingly, other mycobacterial factors are also involved in mycobacterial cytosolic translocation, and the co-dependent expression and secretion of EsxA with other factors increases the complexity of dissecting the precise roles of EsxA in mycobacterial pathogenesis [ 43 , 53 , 54 , 55 ]. Moreover, EsxA is a strong immunoregulator and interacts with multiple cellular proteins and signaling pathways [ 35 , 36 , 40 , 56 , 57 , 58 , 59 , 60 ]. In this review, we summarize the current understandings of the diverse roles of EsxA in mycobacterial pathogenesis and regulation of host immune responses, which is followed by a discussion of the challenges and future directions.…”