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Length of dsRNA (poly I:C) drives distinct innate immune responses, depending on the cell type.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2013 Nov; Vol. 94 (5), pp. 1025-36. Date of Electronic Publication: 2013 Aug 02. - Publication Year :
- 2013
-
Abstract
- Poly I:C, a synthetic dsRNA analogue, has been used extensively for decades to study innate responses in vivo and in different cell types. We have found substantial variability while using poly I:C from different sources. In this study we found that poly I:C from 2 commercial sources induced sharply opposite responses in myeloid and fibroblasts, depending on the length of the poly I:C. Although short poly I:C (≈ 1-1.5 kb) induced greater amounts of TNF-α, IL-8, and IFN-β and a stronger antiviral response in myeloid cells, it was a poor inducer in fibroblasts. By contrast, long poly I:C (>5 kb) preferentially elicited higher cytokine and antiviral responses in fibroblasts and showed diminished responses in myeloid cells. Poly I:C activated NF-κB and STAT-1 signaling in a length- and cell-type-dependent fashion. Mechanistically, short poly I:C was better internalized in the myeloid cells and long poly I:C in the fibroblasts. Finally, long poly I:C required SR-A, whereas short poly I:C required RIG-I and Raftlin. We provide evidence that the length of dsRNA drives distinct innate responses in different cell lineages. These findings may augment in selecting the appropriate poly I:C type to design cell-type-specific potent adjuvants for vaccines against infectious diseases or cancers.
- Subjects :
- Animals
Cells, Cultured
Endocytosis
Interferon Type I biosynthesis
Lipopolysaccharides pharmacology
Membrane Proteins physiology
Mice
Mice, Inbred C57BL
Myeloid Cells drug effects
NF-kappa B physiology
Scavenger Receptors, Class A physiology
Tumor Necrosis Factor-alpha biosynthesis
Immunity, Innate drug effects
Immunologic Factors pharmacology
Poly I-C pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1938-3673
- Volume :
- 94
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 23911868
- Full Text :
- https://doi.org/10.1189/jlb.0312125