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Int. J. Mol. Sci. 2018, 19(5), 1408; https://doi.org/10.3390/ijms19051408

The Bacterial Toxin CNF1 Induces Activation and Maturation of Human Monocyte-Derived Dendritic Cells

1
Department of Immunology and Microbiology, University of Copenhagen, Nørre Alle 14, 2200 Copenhagen, Denmark
2
Italian Center for Global Health, Istituto Superiore di Sanitá; Viale Regina Elena 299, 00161 Rome, Italy
3
Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen, Nørre Alle 14, 2200 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Received: 21 March 2018 / Revised: 4 May 2018 / Accepted: 4 May 2018 / Published: 8 May 2018
(This article belongs to the Special Issue Bacterial Protein Toxins: Enemies within or Unexpected Friends)
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Abstract

Cytotoxic necrotizing factor 1 (CNF1) is a bacterial protein toxin primarily expressed by pathogenic Escherichia coli strains, causing extraintestinal infections. The toxin is believed to enhance the invasiveness of E. coli by modulating the activity of Rho GTPases in host cells, but it has interestingly also been shown to promote inflammation, stimulate host immunity and function as a potent immunoadjuvant. The mechanisms underlying the immunostimulatory properties of CNF1 are, however, poorly characterized, and little is known about the direct effects of the toxin on immune cells. Here, we show that CNF1 induces expression of maturation markers on human immature monocyte-derived dendritic cells (moDCs) without compromising cell viability. Consistent with the phenotypic maturation, CNF1 further triggered secretion of proinflammatory cytokines and increased the capacity of moDCs to stimulate proliferation of allogenic naïve CD4+ T cells. A catalytically inactive form of the toxin did not induce moDC maturation, indicating that the enzymatic activity of CNF1 triggers immature moDCs to undergo phenotypic and functional maturation. As the maturation of dendritic cells plays a central role in initiating inflammation and activating the adaptive immune response, the present findings shed new light on the immunostimulatory properties of CNF1 and may explain why the toxin functions as an immunoadjuvant. View Full-Text
Keywords: CNF1; bacterial toxins; dendritic cells; moDCs; Rho GTPases; cytokine expression; T-cell activation; inflammation; anti-virulence immunity; effector-triggered immunity CNF1; bacterial toxins; dendritic cells; moDCs; Rho GTPases; cytokine expression; T-cell activation; inflammation; anti-virulence immunity; effector-triggered immunity
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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. (CC BY 4.0).
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Gall-Mas, L.; Fabbri, A.; Namini, M.R.J.; Givskov, M.; Fiorentini, C.; Krejsgaard, T. The Bacterial Toxin CNF1 Induces Activation and Maturation of Human Monocyte-Derived Dendritic Cells. Int. J. Mol. Sci. 2018, 19, 1408.

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