Next Article in Journal
Development of Anti-Idiotypic Nanobody-Phage Based Immuno-Loop-Mediated Isothermal Amplification Assay for Aflatoxins in Peanuts
Next Article in Special Issue
Structural and Biochemical Characterization of Botulinum Neurotoxin Subtype B2 Binding to Its Receptors
Previous Article in Journal
A Mediterranean Alexandrium taylorii (Dinophyceae) Strain Produces Goniodomin A and Lytic Compounds but Not Paralytic Shellfish Toxins
Previous Article in Special Issue
Purification, Toxicity and Functional Characterization of a New Proteinaceous Mussel Biotoxin from Bizerte Lagoon
 
Search for Articles:
Title / Keyword
Author / Affiliation
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
Journals
Toxins
Volume 12
Issue 9
10.3390/toxins12090563
toxins-logo
Submit to this Journal Review for this Journal Edit a Special Issue
► Article Menu

Article Menu

share announcement question_answer thumb_up
...
textsms
...
Article

Clostridial C3 Toxins Enter and Intoxicate Human Dendritic Cells

by
Maximilian Fellermann
1,
Christina Huchler
1,
Lea Fechter
1,
Tobias Kolb
1,
Fanny Wondany
2,
Daniel Mayer
3,
Jens Michaelis
2,
Steffen Stenger
3,
Kevin Mellert
4,
Peter Möller
4,
Thomas F. E. Barth
4,
Stephan Fischer
1,* and
Holger Barth
1,*
1
Institute of Pharmacology and Toxicology, University of Ulm Medical Center, 89081 Ulm, Germany
2
Institute of Biophysics, Ulm University, 89081 Ulm, Germany
3
Institute for Medical Microbiology and Hygiene, University of Ulm Medical Center, 89081 Ulm, Germany
4
Institute of Pathology, University of Ulm Medical Center, 89081 Ulm, Germany
*
Authors to whom correspondence should be addressed.
Toxins 2020, 12(9), 563; https://doi.org/10.3390/toxins12090563
Received: 30 July 2020 / Revised: 27 August 2020 / Accepted: 28 August 2020 / Published: 1 September 2020
(This article belongs to the Special Issue Selected Papers from the 26th Meeting of the French Society for Toxinology—Bioengineering of Toxins)
View Full-Text Download PDF
Browse Figures

Abstract

C3 protein toxins produced by Clostridium (C.) botulinum and C. limosum are mono-ADP-ribosyltransferases, which specifically modify the GTPases Rho A/B/C in the cytosol of monocytic cells, thereby inhibiting Rho-mediated signal transduction in monocytes, macrophages, and osteoclasts. C3 toxins are selectively taken up into the cytosol of monocytic cells by endocytosis and translocate from acidic endosomes into the cytosol. The C3-catalyzed ADP-ribosylation of Rho proteins inhibits essential functions of these immune cells, such as migration and phagocytosis. Here, we demonstrate that C3 toxins enter and intoxicate dendritic cells in a time- and concentration-dependent manner. Both immature and mature human dendritic cells efficiently internalize C3 exoenzymes. These findings could also be extended to the chimeric fusion toxin C2IN-C3lim. Moreover, stimulated emission depletion (STED) microscopy revealed the localization of the internalized C3 protein in endosomes and emphasized its potential use as a carrier to deliver foreign proteins into dendritic cells. In contrast, the enzyme C2I from the binary C. botulinum C2 toxin was not taken up into dendritic cells, indicating the specific uptake of C3 toxins. Taken together, we identified human dendritic cells as novel target cells for clostridial C3 toxins and demonstrated the specific uptake of these toxins via endosomal vesicles. View Full-Text
Keywords: dendritic cells; clostridial C3 toxins; cellular uptake; C3botE174Q; fusion toxin C2IN-C3lim; stimulated emission depletion (STED); super-resolution microscopy dendritic cells; clostridial C3 toxins; cellular uptake; C3botE174Q; fusion toxin C2IN-C3lim; stimulated emission depletion (STED); super-resolution microscopy
►▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

SciFeed

Share and Cite

MDPI and ACS Style

Fellermann, M.; Huchler, C.; Fechter, L.; Kolb, T.; Wondany, F.; Mayer, D.; Michaelis, J.; Stenger, S.; Mellert, K.; Möller, P.; Barth, T.F.E.; Fischer, S.; Barth, H. Clostridial C3 Toxins Enter and Intoxicate Human Dendritic Cells. Toxins 2020, 12, 563. https://doi.org/10.3390/toxins12090563

AMA Style

Fellermann M, Huchler C, Fechter L, Kolb T, Wondany F, Mayer D, Michaelis J, Stenger S, Mellert K, Möller P, Barth TFE, Fischer S, Barth H. Clostridial C3 Toxins Enter and Intoxicate Human Dendritic Cells. Toxins. 2020; 12(9):563. https://doi.org/10.3390/toxins12090563

Chicago/Turabian Style

Fellermann, Maximilian, Christina Huchler, Lea Fechter, Tobias Kolb, Fanny Wondany, Daniel Mayer, Jens Michaelis, Steffen Stenger, Kevin Mellert, Peter Möller, Thomas F.E. Barth, Stephan Fischer, and Holger Barth. 2020. "Clostridial C3 Toxins Enter and Intoxicate Human Dendritic Cells" Toxins 12, no. 9: 563. https://doi.org/10.3390/toxins12090563

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Map by Country/Region

1
Back to TopTop