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

Abstract

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.

Autoren

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

DOI

10.3390/ijms22062869

eISSN

1422-0067

Ausgabe der Veröffentlichung

6

Zeitschrift

International Journal of Molecular Sciences

Sprache

en

Online publication date

2021

Paginierung

2869 - 2869

Status

Published online

Herausgeber

MDPI AG

Herausgeber URL

http://dx.doi.org/10.3390/ijms22062869

Datum der Datenerfassung

2023

Titel

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

Ausgabe der Zeitschrift

22

Data source: Crossref

Abstract

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.

Addresses

Department of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.

Autoren

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

DOI

10.3390/ijms22062869

eISSN

1422-0067

Externe Identifier

PubMed Identifier: 33799879
PubMed Central ID: PMC8001596

Funding acknowledgements

DFG: SFB1066, B4 and B5
University Medical Center Mainz: Intramural

Open access

true

ISSN

1422-0067

Ausgabe der Veröffentlichung

6

Zeitschrift

International journal of molecular sciences

Schlüsselwörter

B-Lymphocytes
B-Lymphocyte Subsets
Dendritic Cells
Cells, Cultured
Animals
Mice, Inbred C57BL
Mice, Knockout
Humans
Mice
Dextrans
Receptors, Complement
Drug Carriers
Lymphocyte Activation
Phagocytosis
Complement Activation
Complement System Proteins
Opsonin Proteins
Nanoparticles
CD11b Antigen

Sprache

eng

Medium

Electronic

Online publication date

2021

Open access status

Open Access

Paginierung

2869

Datum der Veröffentlichung

2021

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2021

Titel

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.

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

22

Files

https://www.mdpi.com/1422-0067/22/6/2869/pdf?version=1615545342 https://europepmc.org/articles/PMC8001596?pdf=render

Data source: Europe PubMed Central

Abstract

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.

Date of acceptance

2021

Autoren

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

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/33799879

DOI

10.3390/ijms22062869

eISSN

1422-0067

Externe Identifier

PubMed Central ID: PMC8001596

Funding acknowledgements

DFG: SFB1066, B4 and B5
University Medical Center Mainz: Intramural

Ausgabe der Veröffentlichung

6

Zeitschrift

Int J Mol Sci

Schlüsselwörter

B-1
B-2
carbohydrate surface
complement activation
complement receptor 3
complement receptor 4
dendritic cell
nanocarrier
Animals
B-Lymphocyte Subsets
B-Lymphocytes
CD11b Antigen
Cells, Cultured
Complement Activation
Complement System Proteins
Dendritic Cells
Dextrans
Drug Carriers
Humans
Lymphocyte Activation
Mice, Inbred C57BL
Mice, Knockout
Nanoparticles
Opsonin Proteins
Phagocytosis
Receptors, Complement
Mice

Sprache

eng

Country

Switzerland

PII

ijms22062869

Datum der Veröffentlichung

2021

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2021

Titel

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.

Sub types

Journal Article

Ausgabe der Zeitschrift

22

Data source: PubMed

Author's licence

CC-BY

Autoren

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

Hosting institution

Universitätsbibliothek Mainz

Sammlungen

JGU-Publikationen

Resource version

Published version

DOI

10.3390/ijms22062869

Funding acknowledgements

Open Access-Publizieren Universität Mainz / Universitätsmedizin Mainz

File(s) embargoed

false

Open access

true

ISSN

1422-0067

Ausgabe der Veröffentlichung

6

Zeitschrift

International journal of molecular sciences

Schlüsselwörter

540 Chemie
540 Chemistry and allied sciences
570 Biowissenschaften
570 Life sciences
610 Medizin
610 Medical sciences

Sprache

eng

Open access status

Open Access

Paginierung

2869

Datum der Veröffentlichung

2021

Public URL

https://openscience.ub.uni-mainz.de/handle/20.500.12030/6194

Herausgeber

Molecular Diversity Preservation International

Herausgeber URL

https://doi.org/10.3390/ijms22062869

Datum der Datenerfassung

2021

Datum, an dem der Datensatz öffentlich gemacht wurde

2021

Zugang

Public

Titel

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

Ausgabe der Zeitschrift

22

Files

bednarczyk_monika-complement-ops-20210706181602789.pdf

Data source: OPENSCIENCE.UB

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

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