AUTHOR=Gallant James , Heunis Tiaan , Beltran Caroline , Schildermans Karin , Bruijns Sven , Mertens Inge , Bitter Wilbert , Sampson Samantha L. 

TITLE=PPE38-Secretion-Dependent Proteins of M. tuberculosis Alter NF-kB Signalling and Inflammatory Responses in Macrophages

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.702359

DOI=10.3389/fimmu.2021.702359

ISSN=1664-3224

ABSTRACT=<p>It was previously shown that secretion of PE-PGRS and PPE-MPTR proteins is abolished in clinical <italic>M. tuberculosis</italic> isolates with a deletion in the <italic>ppe38-71</italic> operon, which is associated with increased virulence. Here we investigate the proteins dependent on PPE38 for their secretion and their role in the innate immune response using temporal proteomics and protein turnover analysis in a macrophage infection model. A decreased pro-inflammatory response was observed in macrophages infected with PPE38-deficient <italic>M. tuberculosis</italic> CDC1551 as compared to wild type bacteria. We could show that dampening of the pro-inflammatory response is associated with activation of a RelB/p50 pathway, while the canonical inflammatory pathway is active during infection with wild type <italic>M. tuberculosis</italic> CDC1551. These results indicate a molecular mechanism by which <italic>M. tuberculosis</italic> PE/PPE proteins controlled by PPE38 have an effect on modulating macrophage responses through NF-kB signalling.</p>