TY - JOUR
T1 - Group A Streptococcus establishes pharynx infection by degrading the deoxyribonucleic acid of neutrophil extracellular traps
AU - Tanaka, Mototsugu
AU - Kinoshita-Daitoku, Ryo
AU - Kiga, Kotaro
AU - Sanada, Takahito
AU - Zhu, Bo
AU - Okano, Tokuju
AU - Aikawa, Chihiro
AU - Iida, Tamako
AU - Ogura, Yoshitoshi
AU - Hayashi, Tetsuya
AU - Okubo, Koshu
AU - Kurosawa, Miho
AU - Hirahashi, Junichi
AU - Suzuki, Toshihiko
AU - Nakagawa, Ichiro
AU - Nangaku, Masaomi
AU - Mimuro, Hitomi
N1 - Funding Information:
We would like to thank Dr. Paul Patrick Cleary (University of Minnesota, USA) for technical instruction for nasal infection, and Dr Yasuteru Urano (Graduate School of Medicine, University of Tokyo, Japan) for useful experimental discussions. This work was supported by JSPS KAKENHI Grant Number JP15H06158, JP17K14974 (M.T.); JP16K07083 (T.S.); JP16H05188, JP19H03471 (I.N.) and in part by the Naito Foundation (H.M.).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Group A Streptococcus (GAS) secretes deoxyribonucleases and evades neutrophil extracellular killing by degrading neutrophil extracellular traps (NETs). However, limited information is currently available on the interaction between GAS and NETs in the pathogenicity of GAS pharyngitis. In this study, we modified a mouse model of GAS pharyngitis and revealed an essential role for DNase in this model. After intranasal infection, the nasal mucosa was markedly damaged near the nasal cavity, at which GAS was surrounded by neutrophils. When neutrophils were depleted from mice, GAS colonization and damage to the nasal mucosa were significantly decreased. Furthermore, mice infected with deoxyribonuclease knockout GAS mutants (∆spd, ∆endA, and ∆sdaD2) survived significantly better than those infected with wild-type GAS. In addition, the supernatants of digested NETs enhanced GAS-induced cell death in vitro. Collectively, these results indicate that NET degradation products may contribute to the establishment of pharyngeal infection caused by GAS.
AB - Group A Streptococcus (GAS) secretes deoxyribonucleases and evades neutrophil extracellular killing by degrading neutrophil extracellular traps (NETs). However, limited information is currently available on the interaction between GAS and NETs in the pathogenicity of GAS pharyngitis. In this study, we modified a mouse model of GAS pharyngitis and revealed an essential role for DNase in this model. After intranasal infection, the nasal mucosa was markedly damaged near the nasal cavity, at which GAS was surrounded by neutrophils. When neutrophils were depleted from mice, GAS colonization and damage to the nasal mucosa were significantly decreased. Furthermore, mice infected with deoxyribonuclease knockout GAS mutants (∆spd, ∆endA, and ∆sdaD2) survived significantly better than those infected with wild-type GAS. In addition, the supernatants of digested NETs enhanced GAS-induced cell death in vitro. Collectively, these results indicate that NET degradation products may contribute to the establishment of pharyngeal infection caused by GAS.
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U2 - 10.1038/s41598-020-60306-w
DO - 10.1038/s41598-020-60306-w
M3 - Article
C2 - 32094510
AN - SCOPUS:85079746896
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 3251
ER -