Please use this identifier to cite or link to this item:
Authors: Bednarczyk, Monika
Medina-Montano, Carolina
Fittler, Frederic Julien
Stege, Henner
Roskamp, Meike
Kuske, Michael
Langer, Christian
Vahldieck, Marco
Montermann, Evelyn
Tubbe, Ingrid
Röhrig, Nadine
Dzionek, Andrzej
Grabbe, Stephan
Bros, Matthias
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
Online publication date: 9-Jul-2021
Language: english
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.
DDC: 540 Chemie
540 Chemistry and allied sciences
570 Biowissenschaften
570 Life sciences
610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
Document type specification: Scientific article
License: CC BY
Information on rights of use:
Journal: International journal of molecular sciences
Pages or article number: 2869
Publisher: Molecular Diversity Preservation International
Publisher place: Basel
Issue date: 2021
ISSN: 1422-0067
Publisher URL:
Publisher DOI: 10.3390/ijms22062869
Appears in collections:JGU-Publikationen

Files in This Item:
  File Description SizeFormat
bednarczyk_monika-complement-ops-20210706181602789.pdf3.74 MBAdobe PDFView/Open