Autoren:	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
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
Online-Publikationsdatum:	9-Jul-2021
Erscheinungsdatum:	2021
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	540 Chemie 540 Chemistry and allied sciences 570 Biowissenschaften 570 Life sciences 610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-6185
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Weitere Angaben zur Dokumentart:	Scientific article
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	International journal of molecular sciences 22 6
Seitenzahl oder Artikelnummer:	2869
Verlag:	Molecular Diversity Preservation International
Verlagsort:	Basel
Erscheinungsdatum:	2021
ISSN:	1422-0067 1661-6596
URL der Originalveröffentlichung:	https://doi.org/10.3390/ijms22062869
DOI der Originalveröffentlichung:	10.3390/ijms22062869
Enthalten in den Sammlungen:	JGU-Publikationen