Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation

The mechanisms that underlie the potent Th1-adjuvant capacity of poly(methyl vinyl ether-co-maleic anhydride) nanoparticles (NPs) were investigated. Traditionally, polymer NPs have been considered delivery systems that promote a closer interaction between antigen and antigen-presenting cells (APCs...

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Main Authors: Tamayo, I. (Ibai), Irache, J.M. (Juan Manuel), Mansilla, C. (Cristina), Ochoa-Repáraz, J. (Javier), Lasarte, J.J. (Juan José), Gamazo, C. (Carlos)
Format: info:eu-repo/semantics/article
Language:eng
Published: American Society of Microbiology 2011
Subjects:
Online Access:https://hdl.handle.net/10171/17103
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author Tamayo, I. (Ibai)
Irache, J.M. (Juan Manuel)
Mansilla, C. (Cristina)
Ochoa-Repáraz, J. (Javier)
Lasarte, J.J. (Juan José)
Gamazo, C. (Carlos)
author_facet Tamayo, I. (Ibai)
Irache, J.M. (Juan Manuel)
Mansilla, C. (Cristina)
Ochoa-Repáraz, J. (Javier)
Lasarte, J.J. (Juan José)
Gamazo, C. (Carlos)
author_sort Tamayo, I. (Ibai)
collection DSpace
description The mechanisms that underlie the potent Th1-adjuvant capacity of poly(methyl vinyl ether-co-maleic anhydride) nanoparticles (NPs) were investigated. Traditionally, polymer NPs have been considered delivery systems that promote a closer interaction between antigen and antigen-presenting cells (APCs). Our results revealed that poly(anhydride) NPs also act as agonists of various Toll-like receptors (TLRs) (TLR2, -4, and -5), triggering a Th1-profile cytokine release (gamma interferon [IFN- ], 478 pg/ml versus 39.6 pg/ml from negative control; interleukin-12 [IL-12], 40 pg/ml versus 7.2 pg/ml from negative control) and, after incubation with dendritic cells, inducing a 2.5- to 3.5-fold increase of CD54 and CD86 costimulatory molecule expression. Furthermore, in vivo studies suggest that NPs actively elicit a CD8 T-cell response. Immunization with empty NPs resulted in a significant delay in the mean survival date (from day 7 until day 23 postchallenge) and a protection level of 30% after challenge against a lethal dose of Salmonella enterica serovar Enteritidis. Taken together, our results provide a better understanding of how NPs act as active Th1 adjuvants in immunoprophylaxis and immunotherapy through TLR exploitation.
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spelling oai:dadun.unav.edu:10171-171032020-03-03T19:54:25Z Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation Tamayo, I. (Ibai) Irache, J.M. (Juan Manuel) Mansilla, C. (Cristina) Ochoa-Repáraz, J. (Javier) Lasarte, J.J. (Juan José) Gamazo, C. (Carlos) Nanoparticles Polyanhydride Immunology The mechanisms that underlie the potent Th1-adjuvant capacity of poly(methyl vinyl ether-co-maleic anhydride) nanoparticles (NPs) were investigated. Traditionally, polymer NPs have been considered delivery systems that promote a closer interaction between antigen and antigen-presenting cells (APCs). Our results revealed that poly(anhydride) NPs also act as agonists of various Toll-like receptors (TLRs) (TLR2, -4, and -5), triggering a Th1-profile cytokine release (gamma interferon [IFN- ], 478 pg/ml versus 39.6 pg/ml from negative control; interleukin-12 [IL-12], 40 pg/ml versus 7.2 pg/ml from negative control) and, after incubation with dendritic cells, inducing a 2.5- to 3.5-fold increase of CD54 and CD86 costimulatory molecule expression. Furthermore, in vivo studies suggest that NPs actively elicit a CD8 T-cell response. Immunization with empty NPs resulted in a significant delay in the mean survival date (from day 7 until day 23 postchallenge) and a protection level of 30% after challenge against a lethal dose of Salmonella enterica serovar Enteritidis. Taken together, our results provide a better understanding of how NPs act as active Th1 adjuvants in immunoprophylaxis and immunotherapy through TLR exploitation. 2011-03-18T13:14:09Z 2011-03-18T13:14:09Z 2010 info:eu-repo/semantics/article https://hdl.handle.net/10171/17103 eng info:eu-repo/semantics/openAccess application/pdf American Society of Microbiology
spellingShingle Nanoparticles
Polyanhydride
Immunology
Tamayo, I. (Ibai)
Irache, J.M. (Juan Manuel)
Mansilla, C. (Cristina)
Ochoa-Repáraz, J. (Javier)
Lasarte, J.J. (Juan José)
Gamazo, C. (Carlos)
Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation
title Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation
title_full Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation
title_fullStr Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation
title_full_unstemmed Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation
title_short Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation
title_sort poly(anhydride) nanoparticles act as active th1 adjuvants through toll-like receptor exploitation
topic Nanoparticles
Polyanhydride
Immunology
url https://hdl.handle.net/10171/17103
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