title: Tuning innate immune activation by surface texturing of polymer microparticles: the role of shape in inflammasome activation.
abstract: Polymeric microparticles have been widely investigated as platforms for delivery of drugs, vaccines, and imaging contrast agents and are increasingly used in a variety of clinical applications. Microparticles activate the inflammasome complex and induce the processing and secretion of IL-1β, a key innate immune cytokine. Recent work suggests that although receptors are clearly important for particle phagocytosis, other physical characteristics, especially shape, play an important role in the way microparticles activate cells. We examined the role of particle surface texturing not only on uptake efficiency but also on the subsequent immune cell activation of the inflammasome. Using a method based on emulsion processing of amphiphilic block copolymers, we prepared microparticles with similar overall sizes and surface chemistries but having either smooth or highly microtextured surfaces. In vivo, textured (budding) particles induced more rapid neutrophil recruitment to the injection site. In vitro, budding particles were more readily phagocytosed than smooth particles and induced more lipid raft recruitment to the phagosome. Remarkably, budding particles also induced stronger IL-1β secretion than smooth particles through activation of the NLRP3 inflammasome. These findings demonstrate a pronounced role of particle surface topography in immune cell activation, suggesting that shape is a major determinant of inflammasome activation.
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors: Christine A
authors: CA
authors: Vaine
authors: Milan K
authors: MK
authors: Patel
authors: Jintao
authors: J
authors: Zhu
authors: Eunji
authors: E
authors: Lee
authors: Robert W
authors: RW
authors: Finberg
authors: Ryan C
authors: RC
authors: Hayward
authors: Evelyn A
authors: EA
authors: Kurt-Jones
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010316:Particle Size; D010587:Phagocytosis / Q000276:immunology; D011108:Polymers / Q000737:chemistry; D015398:Signal Transduction; D013499:Surface Properties
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D007375:Interleukin-1; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D011108:Polymers