Proteomics and Network Analyses Reveal Inhibition of Akt-mTOR Signaling in CD4⁺ T Cells by Mycobacterium tuberculosis Mannose-Capped Lipoarabinomannan.

ABSTRACT: Mycobacterium tuberculosis (Mtb) cell wall glycolipid mannose-capped lipoarabinomannan (ManLAM) inhibits CD4⁺ T-cell activation by inhibiting proximal T-cell receptor (TCR) signaling when activated by anti-CD3. To understand the impact of ManLAM on CD4⁺ T-cell function when both the TCR-CD3 complex and major costimulator CD28 are engaged, we performed label-free quantitative MS and network analysis. Mixed-effect model analysis of peptide intensity identified 149 unique peptides representing 131 proteins that were differentially regulated by ManLAM in anti-CD3- and anti-CD28-activated CD4⁺ T cells. Crosstalker, a novel network analysis tool identified dysregulated translation, TCA cycle, and RNA metabolism network modules. PCNA, Akt, mTOR, and UBC were found

SUBMITTER: Karim AF 

PROVIDER: S-EPMC5725663 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature