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Barth H, Fischer S, Möglich A, et al. Clostridial C3 Toxins Target Monocytes/Macrophages and Modulate Their Functions. Front Immunol. 2015;6:339doi: 10.3389/fimmu.2015.00339.
Barth, H., Fischer, S., Möglich, A., & Förtsch, C. (2015). Clostridial C3 Toxins Target Monocytes/Macrophages and Modulate Their Functions. Frontiers in immunology, 6339. https://doi.org/10.3389/fimmu.2015.00339
Barth, Holger, et al. "Clostridial C3 Toxins Target Monocytes/Macrophages and Modulate Their Functions." Frontiers in immunology vol. 6 (2015): 339. doi: https://doi.org/10.3389/fimmu.2015.00339
Barth H, Fischer S, Möglich A, Förtsch C. Clostridial C3 Toxins Target Monocytes/Macrophages and Modulate Their Functions. Front Immunol. 2015 Jun 30;6:339. doi: 10.3389/fimmu.2015.00339. eCollection 2015. PMID: 26175735; PMCID: PMC4485225.
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Front Immunol. 2015 Jun 30;6:339. doi: 10.3389/fimmu.2015.00339. eCollection 2015.

Clostridial C3 Toxins Target Monocytes/Macrophages and Modulate Their Functions.

Frontiers in immunology

Holger Barth, Stephan Fischer, Amelie Möglich, Christina Förtsch

Affiliations

  1. Institute of Pharmacology and Toxicology, University of Ulm Medical Center , Ulm , Germany.
  2. Institute of Pharmacology and Toxicology, University of Ulm Medical Center , Ulm , Germany ; Institute of Organic Chemistry III, University of Ulm , Ulm , Germany.

PMID: 26175735 PMCID: PMC4485225 DOI: 10.3389/fimmu.2015.00339

Abstract

The C3 enzymes from Clostridium (C.) botulinum (C3bot) and Clostridium limosum (C3lim) are single chain protein toxins of about 25 kDa that mono-ADP-ribosylate Rho-A, -B, and -C in the cytosol of mammalian cells. We discovered that both C3 proteins are selectively internalized into the cytosol of monocytes and macrophages by an endocytotic mechanism, comparable to bacterial AB-type toxins, while they are not efficiently taken up into the cytosol of other cell types including epithelial cells and fibroblasts. C3-treatment results in disturbed macrophage functions, such as migration and phagocytosis, suggesting a novel function of clostridial C3 toxins as virulence factors, which selectively interfere with these immune cells. Moreover, enzymatic inactive C3 protein serves as a transport system to selectively deliver pharmacologically active molecules into the cytosol of monocytes/macrophages without damaging these cells. This review addresses also the generation of C3-based molecular tools for experimental macrophage pharmacology and cell biology as well as the exploitation of C3 for development of novel therapeutic strategies against monocyte/macrophage-associated diseases.

Keywords: C3; Rho; cellular uptake; macrophage; targeted drug delivery

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