PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS

Previous studies have shown that single-stranded RNA (ssRNA) mixed with prota-mine forms particles and activates im-mune cells through Toll-like receptors (TLRs). We have found that the size of protamine-RNA particles generated de-pends on the electrolyte content when mixing the 2 components. Moreover, we have evidenced that (1) nanometric par-ticles induce production of interferon-, whereas (2) micrometric particles mainly induce production of tumor necrosis fac-tor- (TNF-) 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- and (2) monocytes that produce TNF- 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 asso-ciated structure in such a way as to trigger the adapted antivirus (nanomet-ric) or antibacterial/antifungal (micromet-ric) immune response. Our results intro-duce a new dimension in danger signaling—how size qualitatively affects innate response. (Blood. 2010;115(22): 4533-4541