The RNA helicase DDX3X is an essential mediator of innate antimicrobial immunity
| العنوان: | The RNA helicase DDX3X is an essential mediator of innate antimicrobial immunity |
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| المؤلفون: | Szappanos, Daniel, Tschismarov, Roland, Perlot, Thomas, Westermayer, Sandra, Fischer, Katrin, Platanitis, Ekaterini, Kallinger, Fabian, Novatchkova, Maria, Lassnig, Caroline, Müller, Mathias, Sexl, Veronika, Bennett, Keiryn L., Foong-Sobis, Michelle, Penninger, Josef M., Decker, Thomas |
| المصدر: | PLoS Pathogens PLoS Pathogens, Vol 14, Iss 11, p e1007397 (2018) |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, B Cells, Physiology, Gene Expression, NK cells, Pathology and Laboratory Medicine, DEAD-box RNA Helicases, Mice, White Blood Cells, Animal Cells, Immune Physiology, Medicine and Health Sciences, Listeriosis, Lymphocytes, Biology (General), Disease Resistance, Mice, Knockout, Innate Immune System, NF-kappa B, Bacterial Pathogens, Killer Cells, Natural, Medical Microbiology, Cytokines, Female, Cellular Types, Pathogens, RNA Helicases, Signal Transduction, Research Article, QH301-705.5, Immune Cells, Immunology, Bone Marrow Cells, Research and Analysis Methods, Microbiology, Sex Factors, Genetics, Animals, Humans, Molecular Biology Techniques, Antibody-Producing Cells, Microbial Pathogens, Molecular Biology, Blood Cells, Macrophages, Biology and Life Sciences, Cell Biology, RC581-607, Fibroblasts, Molecular Development, Listeria Monocytogenes, Immunity, Innate, Hematopoiesis, HEK293 Cells, Immune System, Immunologic diseases. Allergy, Cloning, Developmental Biology |
| الوصف: | DExD/H box RNA helicases, such as the RIG-I-like receptors (RLR), are important components of the innate immune system. Here we demonstrate a pivotal and sex-specific role for the heterosomal isoforms of the DEAD box RNA helicase DDX3 in the immune system. Mice lacking DDX3X during hematopoiesis showed an altered leukocyte composition in bone marrow and spleen and a striking inability to combat infection with Listeria monocytogenes. Alterations in innate immune responses resulted from decreased effector cell availability and function as well as a sex-dependent impairment of cytokine synthesis. Thus, our data provide further in vivo evidence for an essential contribution of a non-RLR DExD/H RNA helicase to innate immunity and suggest it may contribute to sex-related differences in resistance to microbes and resilience to inflammatory disease. Author summary The establishment of innate immunity to pathogens requires cells to sense microbial molecules and to initiate a de novo transcription-based antimicrobial response. With the identification of Rig I and Mda5, two RNA helicases were shown to serve as pivotal receptors of viral RNA. Subsequently, a considerable number of RNA helicases were proposed to function as sensors or signal transducers for both microbial RNA and DNA. X-chromosome-encoded RNA helicase DDX3X was discovered as an interactor of the S/T kinase TBK1 which regulates the production of type I Interferons (IFN-I). However, the importance of DDX3X for innate immunity in an organismic context remained elusive. Here we describe and analyze mice lacking DDX3X in hematopoietic cells. We show contributions of DDX3X to hematopoiesis and a striking loss in resistance against Listeria monocytogenes. Our data reveal that DDX3X is critically involved in enhancing the expression of numerous antimicrobial genes. Consistently, production of important cytokines such as IL12 or IFNγ is reduced. Furthermore, DDX3X-deficient macrophages show reduced ability to restrict L. monocytogenes growth. Owing to partial redundancy with its close Y-chromosomal homologue, DDX3Y, the observed effects differ between mouse sexes. Thus, DDX3X may contribute to sex differences in immunity to pathogens and inflammatory disease. |
| وصف الملف: | application/pdf |
| تدمد: | 1553-7374 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::c2f737b6a901357cc657fd3878591b6dTest https://pubmed.ncbi.nlm.nih.gov/30475900Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....c2f737b6a901357cc657fd3878591b6d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 |
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