| First Author | Rettig L | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 22 | Pages | 4533-41 |
| PubMed ID | 20304804 | Mgi Jnum | J:161556 |
| Mgi Id | MGI:4459607 | Doi | 10.1182/blood-2009-11-247817 |
| Citation | Rettig L, et al. (2010) Particle size and activation threshold: a new dimension of danger signaling. Blood 115(22):4533-41 |
| abstractText | Previous studies have shown that single-stranded RNA (ssRNA) mixed with protamine forms particles and activates immune cells through Toll-like receptors (TLRs). We have found that the size of protamine-RNA particles generated depends on the electrolyte content when mixing the 2 components. Moreover, we have evidenced that (1) nanometric particles induce production of interferon-alpha, whereas (2) micrometric particles mainly induce production of tumor necrosis factor-alpha (TNF-alpha) in human immune cells. We found that the mechanisms underlying these observations are (1) nanoparticles but not microparticles are selectively phagocytosed by plasmacytoid dendritic cells (pDCs), which produce interferon-alpha and (2) monocytes that produce TNF-alpha have a higher activation threshold than that of pDCs. Thus, at the same time as sensing pathogen-associated molecular patterns such as ssRNA, the immune system distinguishes the size of the associated structure in such a way as to trigger the adapted antivirus (nanometric) or antibacterial/antifungal (micrometric) immune response. Our results introduce a new dimension in danger signaling--how size qualitatively affects innate response. |
