Complement-Opsonized Nano-Carriers are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells
The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellu...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-03-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/6/2869 |
id |
doaj-10907085291e4a978fdeadebda762cd7 |
---|---|
record_format |
Article |
spelling |
doaj-10907085291e4a978fdeadebda762cd72021-03-12T00:06:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01222869286910.3390/ijms22062869Complement-Opsonized Nano-Carriers are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 CellsMonika Bednarczyk0Carolina Medina-Montano1Frederic Julien Fittler2Henner Stege3Meike Roskamp4Michael Kuske5Christian Langer6Marco Vahldieck7Evelyn Montermann8Ingrid Tubbe9Nadine Röhrig10Andrzej Dzionek11Stephan Grabbe12Matthias Bros13Department of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, GermanyMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429 Bergisch Gladbach, GermanyDepartment of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, GermanyMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429 Bergisch Gladbach, GermanyMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429 Bergisch Gladbach, GermanyDepartment of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, GermanyMiltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429 Bergisch Gladbach, GermanyDepartment of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, GermanyThe development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.https://www.mdpi.com/1422-0067/22/6/2869nanocarriercarbohydrate surfacecomplement activationcomplement receptor 3complement receptor 4dendritic cell |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Monika Bednarczyk Carolina Medina-Montano Frederic Julien Fittler Henner Stege Meike Roskamp Michael Kuske Christian Langer Marco Vahldieck Evelyn Montermann Ingrid Tubbe Nadine Röhrig Andrzej Dzionek Stephan Grabbe Matthias Bros |
spellingShingle |
Monika Bednarczyk Carolina Medina-Montano Frederic Julien Fittler Henner Stege Meike Roskamp Michael Kuske Christian Langer Marco Vahldieck Evelyn Montermann Ingrid Tubbe Nadine Röhrig Andrzej Dzionek Stephan Grabbe Matthias Bros Complement-Opsonized Nano-Carriers are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells International Journal of Molecular Sciences nanocarrier carbohydrate surface complement activation complement receptor 3 complement receptor 4 dendritic cell |
author_facet |
Monika Bednarczyk Carolina Medina-Montano Frederic Julien Fittler Henner Stege Meike Roskamp Michael Kuske Christian Langer Marco Vahldieck Evelyn Montermann Ingrid Tubbe Nadine Röhrig Andrzej Dzionek Stephan Grabbe Matthias Bros |
author_sort |
Monika Bednarczyk |
title |
Complement-Opsonized Nano-Carriers are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells |
title_short |
Complement-Opsonized Nano-Carriers are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells |
title_full |
Complement-Opsonized Nano-Carriers are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells |
title_fullStr |
Complement-Opsonized Nano-Carriers are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells |
title_full_unstemmed |
Complement-Opsonized Nano-Carriers are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells |
title_sort |
complement-opsonized nano-carriers are bound by dendritic cells (dc) via complement receptor (cr)3, and by b cell subpopulations via cr-1/2, and affect the activation of dc and b-1 cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-03-01 |
description |
The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses. |
topic |
nanocarrier carbohydrate surface complement activation complement receptor 3 complement receptor 4 dendritic cell |
url |
https://www.mdpi.com/1422-0067/22/6/2869 |
work_keys_str_mv |
AT monikabednarczyk complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT carolinamedinamontano complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT fredericjulienfittler complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT hennerstege complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT meikeroskamp complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT michaelkuske complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT christianlanger complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT marcovahldieck complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT evelynmontermann complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT ingridtubbe complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT nadinerohrig complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT andrzejdzionek complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT stephangrabbe complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells AT matthiasbros complementopsonizednanocarriersareboundbydendriticcellsdcviacomplementreceptorcr3andbybcellsubpopulationsviacr12andaffecttheactivationofdcandb1cells |
_version_ |
1724223240126070784 |