This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Open AccessArticle
Macropinocytosis Is the Principal Uptake Mechanism of Antigen-Presenting Cells for Allergen-Specific Virus-like Nanoparticles
by
Armin Kraus
Armin Kraus 1
,
Bernhard Kratzer
Bernhard Kratzer 1
,
Al Nasar Ahmed Sehgal
Al Nasar Ahmed Sehgal 1,
Doris Trapin
Doris Trapin 1,
Matarr Khan
Matarr Khan 1,
Nicole Boucheron
Nicole Boucheron 1 and
Winfried F. Pickl
Winfried F. Pickl 1,2,*
1
Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
2
Karl Landsteiner University of Health Sciences, 3500 Krems, Austria
*
Author to whom correspondence should be addressed.
Vaccines 2024, 12(7), 797; https://doi.org/10.3390/vaccines12070797 (registering DOI)
Submission received: 23 May 2024
/
Revised: 29 June 2024
/
Accepted: 12 July 2024
/
Published: 18 July 2024
Abstract
Virus-like nanoparticles (VNP) are regarded as efficient vaccination platforms and have proven to be useful for the non-anaphylactogenic delivery of allergen-specific immunotherapy in preclinical models previously. Herein, we sought to determine the mode of VNP uptake by antigen presenting cells (APC). Accordingly, we screened a collection of substances known to inhibit different uptake pathways by APC. The human leukemia monocytic cell line THP-1 and the murine dendritic cell line DC 2.4 were examined for the uptake of fluorescently labelled VNP in the presence or absence of inhibitors. The inhibitory effect of candidate substances that blocked VNP uptake in APC lines was subsequently evaluated in studies with primary APC present in splenocyte and lung cell homogenates in vitro and upon intratracheal application of VNP in vivo. The uptake of allergen-specific VNP in vitro and in vivo was mainly observed by macrophages and CD103+ dendritic cells and was sensitive to inhibitors that block macropinocytosis, such as hyperosmolarity induced by sucrose or the polyphenol compound Rottlerin at low micromolar concentrations but not by other inhibitors. Also, T-cell proliferation induced by allergen-specific VNP was significantly reduced by both substances. In contrast, substances that stimulate macropinocytosis, such as Heparin and phorbol myristate acetate (PMA), increased VNP-uptake and may, thus, help modulate allergen-specific T-cell responses. We have identified macropinocytosis as the principal uptake mechanism of APC for allergen-specific VNP in vitro and in vivo, paving the way for further improvement of VNP-based therapies, especially those that can be used for tolerance induction in allergy, in the future.
Share and Cite
MDPI and ACS Style
Kraus, A.; Kratzer, B.; Sehgal, A.N.A.; Trapin, D.; Khan, M.; Boucheron, N.; Pickl, W.F.
Macropinocytosis Is the Principal Uptake Mechanism of Antigen-Presenting Cells for Allergen-Specific Virus-like Nanoparticles. Vaccines 2024, 12, 797.
https://doi.org/10.3390/vaccines12070797
AMA Style
Kraus A, Kratzer B, Sehgal ANA, Trapin D, Khan M, Boucheron N, Pickl WF.
Macropinocytosis Is the Principal Uptake Mechanism of Antigen-Presenting Cells for Allergen-Specific Virus-like Nanoparticles. Vaccines. 2024; 12(7):797.
https://doi.org/10.3390/vaccines12070797
Chicago/Turabian Style
Kraus, Armin, Bernhard Kratzer, Al Nasar Ahmed Sehgal, Doris Trapin, Matarr Khan, Nicole Boucheron, and Winfried F. Pickl.
2024. "Macropinocytosis Is the Principal Uptake Mechanism of Antigen-Presenting Cells for Allergen-Specific Virus-like Nanoparticles" Vaccines 12, no. 7: 797.
https://doi.org/10.3390/vaccines12070797
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details
here.
Article Metrics
Article metric data becomes available approximately 24 hours after publication online.