Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages.

Abstract:

:Mycobacterial infection leads to activation of the RIG-I/MAVS/TBK1 RNA sensing pathway in macrophages but the consequences of this activation remains poorly defined. In this study, we determined that activation of this RNA sensing pathway stimulates ICAM-1 expression in M.avium-infected macrophage through the inhibition of the E3 ubiquitin ligase CRL4COP1/DET1. CRL4 when active targets the transcription factor ETV5 for degradation by the ubiquitin-proteasome system. In the absence of the ETV5 transcription factor, ICAM-1 expression is significantly decreased. The M.avium-induced ICAM-1 production is required for the formation of immune synapse between infected macrophages and antigen-specific CD4+ T lymphocytes, and is essential for CD4+ T lymphocyte-mediated mycobacterial killing in vitro and in mice. This study demonstrates a previously undefined mechanism by which a host cytosolic RNA sensing pathway contributes to the interplay between mycobacteria infected macrophages and antigen-specific T lymphocytes.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Cheng Y,Kiene NJ,Tatarian A,Eix EF,Schorey JS

doi

10.1371/journal.ppat.1008569

subject

Has Abstract

pub_date

2020-05-28 00:00:00

pages

e1008569

issue

5

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-20-00043

journal_volume

16

pub_type

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