Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages.
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 t...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-05-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008569 |
| _version_ | 1818537664083656704 |
|---|---|
| author | Yong Cheng Nicholas J Kiene Alexandra Tatarian Emily F Eix Jeffrey S Schorey |
| author_facet | Yong Cheng Nicholas J Kiene Alexandra Tatarian Emily F Eix Jeffrey S Schorey |
| author_sort | Yong Cheng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T18:53:40Z |
| format | Article |
| id | doaj.art-e4b6f650abc24109962c0e512db9d436 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-11T18:53:40Z |
| publishDate | 2020-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-e4b6f650abc24109962c0e512db9d4362022-12-22T00:54:13ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-05-01165e100856910.1371/journal.ppat.1008569Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages.Yong ChengNicholas J KieneAlexandra TatarianEmily F EixJeffrey S SchoreyMycobacterial 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.https://doi.org/10.1371/journal.ppat.1008569 |
| spellingShingle | Yong Cheng Nicholas J Kiene Alexandra Tatarian Emily F Eix Jeffrey S Schorey Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages. PLoS Pathogens |
| title | Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages. |
| title_full | Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages. |
| title_fullStr | Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages. |
| title_full_unstemmed | Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages. |
| title_short | Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages. |
| title_sort | host cytosolic rna sensing pathway promotes t lymphocyte mediated mycobacterial killing in macrophages |
| url | https://doi.org/10.1371/journal.ppat.1008569 |
| work_keys_str_mv | AT yongcheng hostcytosolicrnasensingpathwaypromotestlymphocytemediatedmycobacterialkillinginmacrophages AT nicholasjkiene hostcytosolicrnasensingpathwaypromotestlymphocytemediatedmycobacterialkillinginmacrophages AT alexandratatarian hostcytosolicrnasensingpathwaypromotestlymphocytemediatedmycobacterialkillinginmacrophages AT emilyfeix hostcytosolicrnasensingpathwaypromotestlymphocytemediatedmycobacterialkillinginmacrophages AT jeffreysschorey hostcytosolicrnasensingpathwaypromotestlymphocytemediatedmycobacterialkillinginmacrophages |