TY - JOUR
T1 - PPE38-Secretion-Dependent Proteins of M. tuberculosis Alter NF-kB Signalling and Inflammatory Responses in Macrophages
AU - Gallant, James
AU - Heunis, Tiaan
AU - Beltran, Caroline
AU - Schildermans, Karin
AU - Bruijns, Sven
AU - Mertens, Inge
AU - Bitter, Wilbert
AU - Sampson, Samantha L.
N1 - Funding Information: JG would like to acknowledge the NRF for financial support under the NRF-VU Desmond Tutu Doctoral training program and the Harry Crossley Foundation for project support. TH was supported by a South African National Research Foundation-Department of Science and Technology Innovation Postdoctoral Publisher Copyright: © Copyright © 2021 Gallant, Heunis, Beltran, Schildermans, Bruijns, Mertens, Bitter and Sampson. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7/2
Y1 - 2021/7/2
N2 - It was previously shown that secretion of PE-PGRS and PPE-MPTR proteins is abolished in clinical M. tuberculosis isolates with a deletion in the ppe38-71 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 M. tuberculosis 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 M. tuberculosis CDC1551. These results indicate a molecular mechanism by which M. tuberculosis PE/PPE proteins controlled by PPE38 have an effect on modulating macrophage responses through NF-kB signalling.
AB - It was previously shown that secretion of PE-PGRS and PPE-MPTR proteins is abolished in clinical M. tuberculosis isolates with a deletion in the ppe38-71 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 M. tuberculosis 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 M. tuberculosis CDC1551. These results indicate a molecular mechanism by which M. tuberculosis PE/PPE proteins controlled by PPE38 have an effect on modulating macrophage responses through NF-kB signalling.
KW - Mycobacterium tuberculosis
KW - NF-KB signalling
KW - PE/PPE
KW - macrophage
KW - proteomics
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85110472357&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34276695
UR - http://www.scopus.com/inward/record.url?scp=85110472357&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85110472357&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2021.702359
DO - https://doi.org/10.3389/fimmu.2021.702359
M3 - Article
C2 - 34276695
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 702359
ER -
