Particle size and activation threshold: a new dimension of danger signaling
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Particle size and activation threshold: a new dimension of danger signaling. / Rettig, Lorna; Haen, Sebastian P; Bittermann, Anne Greet; von Boehmer, Lotta; Curioni, Alessandra; Krämer, Stefanie D; Knuth, Alexander; Pascolo, Steve.
in: BLOOD, Jahrgang 115, Nr. 22, 03.06.2010, S. 4533-41.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Particle size and activation threshold: a new dimension of danger signaling
AU - Rettig, Lorna
AU - Haen, Sebastian P
AU - Bittermann, Anne Greet
AU - von Boehmer, Lotta
AU - Curioni, Alessandra
AU - Krämer, Stefanie D
AU - Knuth, Alexander
AU - Pascolo, Steve
PY - 2010/6/3
Y1 - 2010/6/3
N2 - 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.
AB - 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.
KW - Adjuvants, Immunologic/chemistry
KW - Animals
KW - Base Sequence
KW - Dendritic Cells/immunology
KW - Humans
KW - Immunity, Innate
KW - In Vitro Techniques
KW - Interferon-alpha/biosynthesis
KW - Membrane Glycoproteins/deficiency
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Nanoparticles/chemistry
KW - Oligodeoxyribonucleotides/chemistry
KW - Particle Size
KW - Phagocytosis
KW - Protamines/chemistry
KW - RNA/chemistry
KW - RNA Stability
KW - Signal Transduction/genetics
KW - Toll-Like Receptor 7/deficiency
KW - Tumor Necrosis Factor-alpha/biosynthesis
U2 - 10.1182/blood-2009-11-247817
DO - 10.1182/blood-2009-11-247817
M3 - SCORING: Journal article
C2 - 20304804
VL - 115
SP - 4533
EP - 4541
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 22
ER -
