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Group A streptococcal DNase Sda1 impairs plasmacytoid dendritic cell's type I interferon response


Keller, Nadia; Woytschak, Janine; Martin Heeb, Lukas Erwin; Maggio, Ewerton Marques; Shambat, Srikanth Mairpady; Snäll, Johanna; Hyldegaard, Ole; Boyman, Onur; Norrby-Teglund, Anna; Zinkernagel, Annelies Sophie (2019). Group A streptococcal DNase Sda1 impairs plasmacytoid dendritic cell's type I interferon response. Journal of Investigative Dermatology, 139(6):1284-1293.

Abstract

Group A Streptococcus causes severe invasive infections, including necrotizing fasciitis. The expression of an array of virulence factors targeting specific host immune functions impedes successful bacterial clearance. The virulence factor streptococcal DNase Sda1 was previously shown to interfere with the entrapment of bacteria through neutrophil extracellular traps and TLR9 signaling. In this study, we showed that plasmacytoid dendritic cells are recruited to the infected tissue during group A streptococcal necrotizing fasciitis. We found that the streptococcal DNase Sda1 impairs plasmacytoid dendritic cells recruitment by reducing IFN-1 levels at the site of infection. We found that streptococcal DNase Sda1 interferes with stabilization of the DNA by the host molecule High Mobility Group Box1 protein, which may account for decreased IFN-1 levels at the site of infection.

Abstract

Group A Streptococcus causes severe invasive infections, including necrotizing fasciitis. The expression of an array of virulence factors targeting specific host immune functions impedes successful bacterial clearance. The virulence factor streptococcal DNase Sda1 was previously shown to interfere with the entrapment of bacteria through neutrophil extracellular traps and TLR9 signaling. In this study, we showed that plasmacytoid dendritic cells are recruited to the infected tissue during group A streptococcal necrotizing fasciitis. We found that the streptococcal DNase Sda1 impairs plasmacytoid dendritic cells recruitment by reducing IFN-1 levels at the site of infection. We found that streptococcal DNase Sda1 interferes with stabilization of the DNA by the host molecule High Mobility Group Box1 protein, which may account for decreased IFN-1 levels at the site of infection.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 June 2019
Deposited On:29 Jan 2019 12:03
Last Modified:08 Jul 2019 14:09
Publisher:Elsevier
ISSN:0022-202X
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jid.2018.11.027
PubMed ID:30543898

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