title: Immunostimulatory activity of polysaccharide-poly(I:C) nanoparticles.
abstract: Immunostimulatory properties of mushroom derived polysaccharides (PS) as stand-alone agents were tested. Next, PS were nanocomplexed with polyI:C (pIC) to yield stable nanoparticles around 200 nm in size evidenced by atomic force microscopy and dynamic light scattering analyses. PSs were selectively engaged by cells expressing TLR2 and initiated NFκB dependent signaling cascade leading to a Th1-biased cytokine/chemokine secretion in addition to bactericidal nitric oxide (NO) production from macrophages. Moreover, cells treated with nanoparticles led to synergistic IL6, production and upregulation of TNFα, MIP3α, IFNγ and IP10 transcript expression. In mice, PS-Ovalbumin-pIC formulation surpassed anti-OVA IgG responses when compared to either PS-OVA or pIC-OVA mediated immunity. Our results revealed that signal transduction initiated both by TLR2 and TLR3 via co-delivery of pIC by PS in nanoparticle depot delivery system is an effective immunization strategy. The present work implicate that the PS and nucleic acid based nanoparticle approach along with protein antigens can be harnessed to prevent infectious diseases.
authors: Biotherapeutic ODN Research Laboratory, Molecular Biology and Genetics Department, Faculty of Sciences, Bilkent University, Bilkent, Ankara 06800, Turkey.
authors: Gizem
authors: G
authors: Tincer
authors: Seda
authors: S
authors: Yerlikaya
authors: Fuat C
authors: FC
authors: Yagci
authors: Tamer
authors: T
authors: Kahraman
authors: Osman M
authors: OM
authors: Atanur
authors: Oktay
authors: O
authors: Erbatur
authors: Ihsan
authors: I
authors: Gursel
mesh_terms: D000276:Adjuvants, Immunologic; D000363:Agaricales / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007114:Immunization; D007369:Interferon Inducers / Q000276:immunology*; D019410:Interleukin-16 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology*; D011134:Polysaccharides / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D007369:Interferon Inducers; D019410:Interleukin-16; D020382:Interleukin-18; D011134:Polysaccharides; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011070:Poly I-C