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

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

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Article number702359
JournalFrontiers in Immunology
Publication statusPublished - 2 Jul 2021

Bibliographical note

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 2021 Elsevier B.V., All rights reserved.


  • macrophage
  • Mycobacterium tuberculosis
  • NF-KB signalling
  • PE/PPE
  • proteomics


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