An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity
| Autor: | Jeffrey D. Hasday, Xiaoling Li, Stefanie N. Vogel, Saroj Kant Mohapatra, Alan S. Cross, Heather J. Ezelle, Janette M. Harro, Bret A. Hassel, Oswald Crasta, Kari Ann Shirey, Lei Zhang, Tae Jin Kang |
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| Rok vydání: | 2008 |
| Předmět: |
RNase P
RNA Stability Immunology Endoribonuclease Endosomes Biology Cathepsin E Biochemistry Gene Expression Regulation Enzymologic Proinflammatory cytokine Microbiology Anthrax Mice Mediator Immune system Immunity Endoribonucleases Escherichia coli Animals Immunology and Allergy Molecular Biology Escherichia coli Infections Mice Knockout Multidisciplinary Innate immune system Antibacterial Response Hematology Biological Sciences Virology Bacillus anthracis Interferon Type I Antibacterial activity |
| Zdroj: | Proceedings of the National Academy of Sciences. 105:20816-20821 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Type I IFNs were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of IFN antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of IFN-induced antiviral activity. Here, we identify a role for RNase-L in the host antibacterial response. RNase-L −/− mice exhibited a dramatic increase in mortality after challenge with Bacillus anthracis and Escherichia coli ; this increased susceptibility was due to a compromised immune response resulting in increased bacterial load. Investigation of the mechanisms of RNase-L antibacterial activity indicated that RNase-L is required for the optimal induction of proinflammatory cytokines that play essential roles in host defense from bacterial pathogens. RNase-L also regulated the expression of the endolysosomal protease, cathepsin-E, and endosome-associated activities, that function to eliminate internalized bacteria and may contribute to RNase-L antimicrobial action. Our results reveal a unique role for RNase-L in the antibacterial response that is mediated through multiple mechanisms. As a regulator of fundamental components of the innate immune response, RNase-L represents a viable therapeutic target to augment host defense against diverse microbial pathogens. |
| Databáze: | OpenAIRE |
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