Length of dsRNA (poly I:C) drives distinct innate immune responses, depending on the cell type
Using short or long Poly I:C to induce optimal innate immune responses or adjuvant effects depends on the target cell types. 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 variabilit...
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Veröffentlicht in: | Journal of leukocyte biology 2013-11, Vol.94 (5), p.1025-1036 |
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Zusammenfassung: | Using short or long Poly I:C to induce optimal innate immune responses or adjuvant effects depends on the target cell types.
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. |
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ISSN: | 0741-5400 1938-3673 |
DOI: | 10.1189/jlb.0312125 |