Biphasic RLR-IFN-beta Response Controls the Balance between Antiviral Immunity and Cell Damage
SCIE
SCOPUS
- Title
- Biphasic RLR-IFN-beta Response Controls the Balance between Antiviral Immunity and Cell Damage
- Authors
- Sun-Young Hwang; Kye-Yeon Hur; Jeong-Rae Kim; Kwang-Hyun Cho; Kim, SH; Yoo, JY
- Date Issued
- 2013-02-01
- Publisher
- The American Association of Immunologists, Inc.
- Abstract
- In RNA virus-infected cells, retinoic acid-inducible gene-I-like receptors (RLRs) sense foreign RNAs and activate signaling cascades to produce IFN-alpha/beta. However, not every infected cell produces IFN-alpha/beta that exhibits cellular heterogeneity in antiviral immune responses. Using the IFN-beta-GFP reporter system, we observed bimodal IFN-beta production in the uniformly stimulated cell population with intracellular dsRNA. Mathematical simulation proposed the strength of autocrine loop via RLR as one of the contributing factor for biphasic IFN-beta expression. Bimodal IFN-beta production with intracellular dsRNA was disturbed by blockage of IFN-alpha/beta secretion or by silencing of the IFN-alpha/beta receptor. Amplification of RLRs was critical in the generation of bimodality of IFN-beta production, because IFN-beta(high) population expressed more RLRs than IFN-beta(low) population. In addition, bimodality in IFN-beta production results in biphasic cellular response against infection, because IFN-beta(high) population was more prone to apoptosis than IFN-beta(low) population. These results suggest that RLR-mediated biphasic cellular response may act to restrict the number of cells expressing IFN-beta and undergoing apoptosis in the infected population. The Journal of Immunology, 2013, 190: 1192-1200.
- Keywords
- POSITIVE-FEEDBACK; RIG-I; DENDRITIC CELLS; REGULATORY FACTOR-7; SIGNALING PATHWAYS; NEGATIVE FEEDBACK; VIRUS-INFECTION; GENE INDUCTION; INTERFERONS; MEMORY
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/14827
- DOI
- 10.4049/JIMMUNOL.1202326
- ISSN
- 0022-1767
- Article Type
- Article
- Citation
- JOURNAL OF IMMUNOLOGY, vol. 190, no. 3, page. 1192 - 1200, 2013-02-01
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