Alginate-coated chitosan nanogel capacity to modulate the effect of TLR ligands on blood dendritic cells.
Biodegradable nanoparticles have been employed for vaccine delivery, frequently admixed with adjuvants. Surprisingly, there is little information on their modulation of immune responses, speculated to be negligible. We analyzed the immunomodulatory capacity of alginate-coated chitosan nanogels (Ng), on porcine and human blood dendritic cells (DCs), when applied with defined adjuvants targeting different DC subpopulations. DC maturation, cytokine production and cell migration were assessed. Ng differentially influenced the immunomodulatory characteristics of individual Toll-like receptor (TLR) ligands: Pam3Cys-SK4-induced IL-1β was enhanced; CpG-oligodeoxynucleotides (CpG-ODN)-induced IFN-α, IL-6 and TNFα were impaired; CpG-ODN-induced CD86 and CCR7, and cell migration, were diminished-plasmacytoid DCs (pDCs) were particularly sensitive. Therein, the Ng influence on DC endocytosis of the TLR ligands was apparently a major contributory element. This demonstrates the importance of predefining the interplay between delivery vehicles and admixed immunostimulatory moieties, for ensuring appropriate immune activation and efficacious combinations.


BACKGROUND
Biodegradable nanoparticles have been utilized in vaccine delivery; however, there is little information available on their immunomodulatory properties, which are thought to be negligible. This study clearly demonstrates that nanogels do influence the developing immune response, which needs to be taken into consideration when utilizing these otherwise very efficacious vaccine delivery approaches.
Institute of Virology and Immunoprophylaxis (IVI), Sensemattstrasse 293, 3147 Mittelhäusern, Switzerland. thomas.demoulins@ivi.admin.ch
Thomas
T
Démoulins
Isabelle
I
Bassi
Lisa
L
Thomann-Harwood
Camilla
C
Jandus
Peter
P
Kaeuper
Hans-Uwe
HU
Simon
Stephan
S
von Gunten
Kenneth C
KC
McCullough
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D001769:Blood / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects; D004705:Endocytosis / Q000235:genetics*; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008024:Ligands; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry; D013552:Swine; D051193:Toll-Like Receptors / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000464:Alginates; D006603:Hexuronic Acids; D008024:Ligands; D000080385:Nanogels; D051193:Toll-Like Receptors; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D020723:Glucuronic Acid; D011094:Polyethyleneimine; D048271:Chitosan
APC; Alg; Blood dendritic cells; CBA; CpG-ODN; CpG-oligodeoxynucleotides; DCs; DMEM; Danger recognition; Dulbecco's modified Eagle's medium; ELISA; FACS; FITC; Immunomodulation; LPS; MFI; MHC; Nanoparticles; Ng; PAMPs; PBMCs; PE; PRRs; TLR; TPP; Toll-like receptor ligands; Toll-like receptors; alginate; allophycocyanin; cDCs; conventional (also known as classical) dendritic cells; cytometric bead array; dendritic cells; enzyme-linked immunosorbent assay; fluorescein isothiocyanate; fluorescence-activated cell sorter; lipopolysaccharide; major histocompatibility complex; mean fluorescence intensity; nanogel; pDCs; pathogen-associated molecular patterns; pathogen-recognition receptors; peripheral blood mononuclear cells; phycoerythrin; plasmacytoid dendritic cells; sodium triphosphate, pentabasic