Formation of Lung Inducible Bronchus Associated Lymphoid Tissue Is Regulated by Mycobacterium tuberculosis Expressed Determinants.

Frontiers in Immunology
Micah D DunlapShabaana A Khader

Abstract

Mycobacterium tuberculosis (Mtb) is the causative agent of the infectious disease tuberculosis (TB), which is a leading cause of death worldwide. Approximately one fourth of the world's population is infected with Mtb. A major unresolved question is delineating the inducers of protective long-lasting immune response without inducing overt, lung inflammation. Previous studies have shown that the presence of inducible Bronchus-Associated Lymphoid Tissue (iBALT) correlate with protection from Mtb infection. In this study, we hypothesized that specific Mtb factors could influence the formation of iBALT, thus skewing the outcome of TB disease. We infected non-human primates (NHPs) with a transposon mutant library of Mtb, and identified specific Mtb mutants that were over-represented within iBALT-containing granulomas. A major pathway reflected in these mutants was Mtb cell wall lipid transport and metabolism. We mechanistically addressed the function of one such Mtb mutant lacking mycobacteria membrane protein large 7 (MmpL7), which transports phthiocerol dimycocerosate (PDIM) to the mycobacterial outer membrane (MOM). Accordingly, murine aerosol infection with the Mtb mutant Δmmpl7 correlated with increased iBALT-containing granulo...Continue Reading

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Citations

Mar 9, 2021·Frontiers in Immunology·Willemijn F RijninkSimone A Joosten

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Methods Mentioned

BETA
confocal microscopy
flow cytometry
ELISA

Software Mentioned

FACS Diva
GraphPad Prism
NIH ImageJ
FlowJo
ImageJ
2iD Imaging

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