4.7 Article

Mycobacterium tuberculosis PPE10 (Rv0442c) alters host cell apoptosis and cytokine profile via linear ubiquitin chain assembly complex HOIP-NF-?B signaling axis

Journal

INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 94, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.intimp.2020.107363

Keywords

Mycobacterium tuberculosis; PPE10; Linear Ubiquitin Chain Assembly Complex; Apoptosis; NF-?B

Funding

  1. National Natural Science Foundation [81871182, 81371851]
  2. National Key Research and Development Program [2016YFC0502304]

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PPE10 plays a significant role in host-pathogen interaction by enhancing Mycobacterium tuberculosis's resistance to stress conditions and regulating host cell apoptosis through the expression of apoptosis-related proteins. The study provides novel insights into the mechanism of action of the PPE gene family.
Tuberculosis caused by Mycobacterium tuberculosis infection remains one of the top ten causes of deaths worldwide. M. tuberculosis genome devoted 10% capacity for highly repeated PE/PPE genes family. To explore the role of PPE10 in host-pathogen interaction, PPE10 encoding gene Rv0442c was heterologously expressed in the nonpathogenic M. smegmatis strain. PPE10 altered the bacterial cell surface properties, colony morphology, and biofilm formation. Ms_PPE10 showed more resistance to stress conditions such as diamide, and low pH, as well as higher survival within the macrophage. Moreover, the host?s cell apoptosis was regulated via decreased expression of caspases, IL-1, IL-6, and TNF-? through the Linear Ubiquitin Chain Assembly Complex (LUBAC) HOIP-NF-?B signaling axis. The study revealed novel insights into the mechanism of action of the PPE family.

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