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An Mtb-Human Protein-Protein Interaction Map Identifies a Switch between Host Antiviral and Antibacterial Responses.

Authors :
Penn BH
Netter Z
Johnson JR
Von Dollen J
Jang GM
Johnson T
Ohol YM
Maher C
Bell SL
Geiger K
Golovkine G
Du X
Choi A
Parry T
Mohapatra BC
Storck MD
Band H
Chen C
Jäger S
Shales M
Portnoy DA
Hernandez R
Coscoy L
Cox JS
Krogan NJ
Source :
Molecular cell [Mol Cell] 2018 Aug 16; Vol. 71 (4), pp. 637-648.e5.
Publication Year :
2018

Abstract

Although macrophages are armed with potent antibacterial functions, Mycobacterium tuberculosis (Mtb) replicates inside these innate immune cells. Determinants of macrophage intrinsic bacterial control, and the Mtb strategies to overcome them, are poorly understood. To further study these processes, we used an affinity tag purification mass spectrometry (AP-MS) approach to identify 187 Mtb-human protein-protein interactions (PPIs) involving 34 secreted Mtb proteins. This interaction map revealed two factors involved in Mtb pathogenesis-the secreted Mtb protein, LpqN, and its binding partner, the human ubiquitin ligase CBL. We discovered that an lpqN Mtb mutant is attenuated in macrophages, but growth is restored when CBL is removed. Conversely, Cbl <superscript>-/-</superscript> macrophages are resistant to viral infection, indicating that CBL regulates cell-intrinsic polarization between antibacterial and antiviral immunity. Collectively, these findings illustrate the utility of this Mtb-human PPI map for developing a deeper understanding of the intricate interactions between Mtb and its host.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-4164
Volume :
71
Issue :
4
Database :
MEDLINE
Journal :
Molecular cell
Publication Type :
Academic Journal
Accession number :
30118682
Full Text :
https://doi.org/10.1016/j.molcel.2018.07.010