Mycobacterium tuberculosis induces immune evasion in macrophages through RNA-binding protein tristetraprolin

Abstract Immune evasion of Mycobacterium tuberculosis (Mtb) facilitates intracellular bacterial growth. The mechanisms immune evasion, however, are still not fully understood. In this study, we reveal that tristetraprolin (TTP), one the best characterized RNA-binding proteins controlling stability target mRNAs, mediates innate mycobacteria. We found TTP knockout mice displayed reduced burden in early stage after Mtb aerosol challenge. Macrophages deficient also showed an inhibition mycobacterial Live mycobacteria induced protein expression macrophages, which was blocked by mTOR inhibitor rapamycin. Rapamycin promoted degradation. Proteasome MG-132 recovered shortened half-life Ubiquitination mediated degradation triggered rapamycin infected macrophages. induction suppressed iNOS/TNF-α/IL-12/IL-23, and weakened bactericidal effects whereas blocking pathway with enhanced macrophages through inhibition. Overall, study reveals a novel role for provides potential host-directed therapy against TB. R21AI171734 & R21AI151936