Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages
| العنوان: | Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages |
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| المؤلفون: | Nicholas J. Kiene, Emily F. Eix, Alexandra Tatarian, Jeffrey S. Schorey, Yong Cheng |
| المصدر: | PLoS Pathogens PLoS Pathogens, Vol 16, Iss 5, p e1008569 (2020) |
| بيانات النشر: | Public Library of Science (PLoS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, Small interfering RNA, Biochemistry, Immunological synapse, Mice, White Blood Cells, Spectrum Analysis Techniques, Animal Cells, Medicine and Health Sciences, Cytotoxic T cell, Macrophage, Small interfering RNAs, Biology (General), Mice, Knockout, 0303 health sciences, biology, T Cells, Chemistry, 030302 biochemistry & molecular biology, Flow Cytometry, Mycobacterium Avium Complex, Cell biology, Ubiquitin ligase, Actinobacteria, Nucleic acids, Spectrophotometry, DEAD Box Protein 58, Cytophotometry, Cellular Types, Research Article, QH301-705.5, Immune Cells, Immunology, Cytotoxic T cells, Protein Serine-Threonine Kinases, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Virology, DNA-binding proteins, Genetics, Animals, Tuberculosis, Non-coding RNA, Molecular Biology, Transcription factor, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Blood Cells, Bacteria, Macrophages, Host Cells, Organisms, Biology and Life Sciences, Proteins, RNA, Cell Biology, T lymphocyte, RC581-607, Gene regulation, Regulatory Proteins, biology.protein, Parasitology, Gene expression, Immunologic diseases. Allergy, Viral Transmission and Infection, Mycobacterium avium, Transcription Factors |
| الوصف: | 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. Author summary As intracellular pathogens mycobacteria illicit a T cell response that is critical for controlling the infection. T cell activation requires not only MHC/peptide and T cell receptor binding but various other receptor-ligand interactions. In the present study we found that activation of the RNA sensing pathway in macrophages infected with M. avium leads to the activation of the transcription factor ETV5 resulting in ICAM-1 expression. ICAM-1 is a known ligand for the T cell LFA-1. We found that the mycobacterial RNA induced expression of ICAM-1 was required for CD4+ T cell binding to M. avium-infected macrophages and for the T cell-mediated killing of the intracellular mycobacteria. Moreover, we found mice deficient in MAVS, a protein required for activation of the cytosolic RNA sensing pathway, were limited in their ability to control an M. avium infection. This loss of control was linked to the loss of ICAM-1 expression by infected alveolar macrophages. In summary, we demonstrate 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. |
| تدمد: | 1553-7374 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8a2cf9271f94c02514b10e288092e736 https://doi.org/10.1371/journal.ppat.1008569 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8a2cf9271f94c02514b10e288092e736 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 |
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