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 Pathogjournal_title
PLoS pathogensauthors
Cheng Y,Kiene NJ,Tatarian A,Eix EF,Schorey JSdoi
10.1371/journal.ppat.1008569subject
Has Abstractpub_date
2020-05-28 00:00:00pages
e1008569issue
5eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-20-00043journal_volume
16pub_type
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