Group A Streptococcal DNase Sda1 Impairs Plasmacytoid Dendritic Cells' Type 1 Interferon Response

Nadia Keller; Janine Woytschak; Lukas Erwin Martin Heeb; Ewerton Marques Maggio; Srikanth Mairpady Shambat; Johanna Snäll; Ole Hyldegaard; Onur Boyman; Anna Norrby-Teglund; Annelies Sophie Zinkernagel

doi:10.1016/j.jid.2018.11.027

Group A Streptococcal DNase Sda1 Impairs Plasmacytoid Dendritic Cells' Type 1 Interferon Response

Nadia Keller, Janine Woytschak, Lukas Erwin Martin Heeb, Ewerton Marques Maggio, Srikanth Mairpady Shambat, Johanna Snäll, Ole Hyldegaard, Onur Boyman, Anna Norrby-Teglund, Annelies Sophie Zinkernagel

Department of Clinical Medicine

3 Citations (Scopus)

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 cell 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 HMGB1 protein, which may account for decreased IFN-1 levels at the site of infection.

Original language	English
Journal	The Journal of Investigative Dermatology
Volume	139
Issue number	6
Pages (from-to)	1284-1293
ISSN	0022-202X
DOIs	https://doi.org/10.1016/j.jid.2018.11.027
Publication status	Published - Jun 2019

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Keller, N., Woytschak, J., Heeb, L. E. M., Marques Maggio, E., Mairpady Shambat, S., Snäll, J., Hyldegaard, O., Boyman, O., Norrby-Teglund, A., & Zinkernagel, A. S. (2019). Group A Streptococcal DNase Sda1 Impairs Plasmacytoid Dendritic Cells' Type 1 Interferon Response. The Journal of Investigative Dermatology, 139(6), 1284-1293. https://doi.org/10.1016/j.jid.2018.11.027

Keller, N, Woytschak, J, Heeb, LEM, Marques Maggio, E, Mairpady Shambat, S, Snäll, J, Hyldegaard, O, Boyman, O, Norrby-Teglund, A & Zinkernagel, AS 2019, 'Group A Streptococcal DNase Sda1 Impairs Plasmacytoid Dendritic Cells' Type 1 Interferon Response', The Journal of Investigative Dermatology, vol. 139, no. 6, pp. 1284-1293. https://doi.org/10.1016/j.jid.2018.11.027

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title = "Group A Streptococcal DNase Sda1 Impairs Plasmacytoid Dendritic Cells' Type 1 Interferon Response",

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 cell 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 HMGB1 protein, which may account for decreased IFN-1 levels at the site of infection.",

author = "Nadia Keller and Janine Woytschak and Heeb, {Lukas Erwin Martin} and {Marques Maggio}, Ewerton and {Mairpady Shambat}, Srikanth and Johanna Sn{\"a}ll and Ole Hyldegaard and Onur Boyman and Anna Norrby-Teglund and Zinkernagel, {Annelies Sophie}",

year = "2019",

month = jun,

doi = "10.1016/j.jid.2018.11.027",

language = "English",

volume = "139",

pages = "1284--1293",

journal = "The Journal of Investigative Dermatology",

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T1 - Group A Streptococcal DNase Sda1 Impairs Plasmacytoid Dendritic Cells' Type 1 Interferon Response

AU - Keller, Nadia

AU - Woytschak, Janine

AU - Heeb, Lukas Erwin Martin

AU - Marques Maggio, Ewerton

AU - Mairpady Shambat, Srikanth

AU - Snäll, Johanna

AU - Hyldegaard, Ole

AU - Boyman, Onur

AU - Norrby-Teglund, Anna

AU - Zinkernagel, Annelies Sophie

PY - 2019/6

Y1 - 2019/6

N2 - 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 cell 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 HMGB1 protein, which may account for decreased IFN-1 levels at the site of infection.

AB - 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 cell 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 HMGB1 protein, which may account for decreased IFN-1 levels at the site of infection.

U2 - 10.1016/j.jid.2018.11.027

DO - 10.1016/j.jid.2018.11.027

M3 - Journal article

C2 - 30543898

SN - 0022-202X

VL - 139

SP - 1284

EP - 1293

JO - The Journal of Investigative Dermatology

JF - The Journal of Investigative Dermatology

IS - 6

ER -

Group A Streptococcal DNase Sda1 Impairs Plasmacytoid Dendritic Cells' Type 1 Interferon Response

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