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J Leukoc Biol. 2013 Nov;94(5):1025-36. doi: 10.1189/jlb.0312125. Epub 2013 Aug 2.

Length of dsRNA (poly I:C) drives distinct innate immune responses, depending on the cell type.

Author information

1
2.Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. ashkara@mcmaster.ca.

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.

KEYWORDS:

antiviral; cytokine; fibroblasts; internalization; myeloid cells

PMID:
23911868
DOI:
10.1189/jlb.0312125
[Indexed for MEDLINE]

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