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Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns
Carbopol is a polyanionic carbomer used in man for topical application and drug delivery purposes. However parenteral administration of Carbopol in animal models results in systemic adjuvant activity including strong pro-inflammatory type-1 T-cell (Th1) polarization. Here we investigated potential p...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850248/ https://www.ncbi.nlm.nih.gov/pubmed/27005810 http://dx.doi.org/10.1016/j.vaccine.2016.03.025 |
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author | Gartlan, Kate H. Krashias, George Wegmann, Frank Hillson, William R. Scherer, Erin M. Greenberg, Philip D. Eisenbarth, Stephanie C. Moghaddam, Amin E. Sattentau, Quentin J. |
author_facet | Gartlan, Kate H. Krashias, George Wegmann, Frank Hillson, William R. Scherer, Erin M. Greenberg, Philip D. Eisenbarth, Stephanie C. Moghaddam, Amin E. Sattentau, Quentin J. |
author_sort | Gartlan, Kate H. |
collection | PubMed |
description | Carbopol is a polyanionic carbomer used in man for topical application and drug delivery purposes. However parenteral administration of Carbopol in animal models results in systemic adjuvant activity including strong pro-inflammatory type-1 T-cell (Th1) polarization. Here we investigated potential pathways of immune activation by Carbopol by comparison with other well-characterized adjuvants. Carbopol administration triggered rapid and robust leukocyte recruitment, pro-inflammatory cytokine secretion and antigen capture largely by inflammatory monocytes. The induction of antigen specific Th1 cells by Carbopol was found to occur via a non-canonical pathway, independent of MyD88/TRIF signaling and in the absence of pattern-recognition-receptor (PRR) activation typically associated with Th1/Ig2a induction. Using multispectral fluorescence imaging (Imagestream) and electron microscopy we demonstrated that phagocytic uptake of Carbopol particles followed by entry into the phagosomal/lysosomal pathway elicited conformational changes to the polymer and reactive oxygen species (ROS) production. We therefore conclude that Carbopol may mediate its adjuvant activity via novel mechanisms of antigen presenting cell activation and Th1 induction, leading to enhanced IgG2a responses independent of microbial pattern recognition. |
format | Online Article Text |
id | pubmed-4850248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48502482016-05-06 Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns Gartlan, Kate H. Krashias, George Wegmann, Frank Hillson, William R. Scherer, Erin M. Greenberg, Philip D. Eisenbarth, Stephanie C. Moghaddam, Amin E. Sattentau, Quentin J. Vaccine Article Carbopol is a polyanionic carbomer used in man for topical application and drug delivery purposes. However parenteral administration of Carbopol in animal models results in systemic adjuvant activity including strong pro-inflammatory type-1 T-cell (Th1) polarization. Here we investigated potential pathways of immune activation by Carbopol by comparison with other well-characterized adjuvants. Carbopol administration triggered rapid and robust leukocyte recruitment, pro-inflammatory cytokine secretion and antigen capture largely by inflammatory monocytes. The induction of antigen specific Th1 cells by Carbopol was found to occur via a non-canonical pathway, independent of MyD88/TRIF signaling and in the absence of pattern-recognition-receptor (PRR) activation typically associated with Th1/Ig2a induction. Using multispectral fluorescence imaging (Imagestream) and electron microscopy we demonstrated that phagocytic uptake of Carbopol particles followed by entry into the phagosomal/lysosomal pathway elicited conformational changes to the polymer and reactive oxygen species (ROS) production. We therefore conclude that Carbopol may mediate its adjuvant activity via novel mechanisms of antigen presenting cell activation and Th1 induction, leading to enhanced IgG2a responses independent of microbial pattern recognition. Elsevier Science 2016-04-27 /pmc/articles/PMC4850248/ /pubmed/27005810 http://dx.doi.org/10.1016/j.vaccine.2016.03.025 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gartlan, Kate H. Krashias, George Wegmann, Frank Hillson, William R. Scherer, Erin M. Greenberg, Philip D. Eisenbarth, Stephanie C. Moghaddam, Amin E. Sattentau, Quentin J. Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns |
title | Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns |
title_full | Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns |
title_fullStr | Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns |
title_full_unstemmed | Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns |
title_short | Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns |
title_sort | sterile inflammation induced by carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850248/ https://www.ncbi.nlm.nih.gov/pubmed/27005810 http://dx.doi.org/10.1016/j.vaccine.2016.03.025 |
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