Streptococcal pyrogenic exotoxin B inhibits apoptotic cell clearance by macrophages through protein S cleavage

Chia Ling Chen, Yueh Ying Wu, Chiou Feng Lin, Chih Feng Kuo, Chia Li Han, Shuying Wang, Woei Jer Chuang, Chiu Yueh Chen, Jiunn Jong Wu, Pei Jane Tsai, Ching Chuan Liu, Yee Shin Lin

Research output: Contribution to journalArticle

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Abstract

Clearance of apoptotic cells by macrophages plays an important role in maintaining tissue homeostasis. Previous study indicated that streptococcal pyrogenic exotoxin B (SPE B) reduces phagocytic activity in group A streptococcus (GAS) infection. Here, we demonstrate that SPE B causes an inhibitory effect on protein S-mediated phagocytosis. In the presence of SPE B, serum- and purified protein S-mediated phagocytosis of apoptotic cells were significantly inhibited. The binding abilities of protein S to apoptotic cells were decreased by treatment with SPE B. Bacterial culture supernatants from GAS NZ131 strain also caused a reduction of protein S binding to apoptotic cells, but speB mutant strain did not. SPE B directly cleaved protein S in vitro and in vivo, whereas a lower level of cleavage occurred in mice infected with a speB isogenic mutant strain. SPE B-mediated initial cleavage of protein S caused a disruption of phagocytosis, and also resulted in a loss of binding ability of protein S-associated C4b-binding protein to apoptotic cells. Taken together, these results suggest a novel pathogenic role of SPE B that initiates protein S degradation followed by the inhibition of apoptotic cell clearance by macrophages.

Original languageEnglish
Article number26026
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 May 16

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Protein S
Macrophages
streptopain
Streptococcus
Phagocytosis
Carrier Proteins
Complement C4b-Binding Protein
Cytophagocytosis
erythrogenic toxin
Protein Binding
Proteolysis
Blood Proteins
Homeostasis
Infection

All Science Journal Classification (ASJC) codes

  • General

Cite this

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title = "Streptococcal pyrogenic exotoxin B inhibits apoptotic cell clearance by macrophages through protein S cleavage",
abstract = "Clearance of apoptotic cells by macrophages plays an important role in maintaining tissue homeostasis. Previous study indicated that streptococcal pyrogenic exotoxin B (SPE B) reduces phagocytic activity in group A streptococcus (GAS) infection. Here, we demonstrate that SPE B causes an inhibitory effect on protein S-mediated phagocytosis. In the presence of SPE B, serum- and purified protein S-mediated phagocytosis of apoptotic cells were significantly inhibited. The binding abilities of protein S to apoptotic cells were decreased by treatment with SPE B. Bacterial culture supernatants from GAS NZ131 strain also caused a reduction of protein S binding to apoptotic cells, but speB mutant strain did not. SPE B directly cleaved protein S in vitro and in vivo, whereas a lower level of cleavage occurred in mice infected with a speB isogenic mutant strain. SPE B-mediated initial cleavage of protein S caused a disruption of phagocytosis, and also resulted in a loss of binding ability of protein S-associated C4b-binding protein to apoptotic cells. Taken together, these results suggest a novel pathogenic role of SPE B that initiates protein S degradation followed by the inhibition of apoptotic cell clearance by macrophages.",
author = "Chen, {Chia Ling} and Wu, {Yueh Ying} and Lin, {Chiou Feng} and Kuo, {Chih Feng} and Han, {Chia Li} and Shuying Wang and Chuang, {Woei Jer} and Chen, {Chiu Yueh} and Wu, {Jiunn Jong} and Tsai, {Pei Jane} and Liu, {Ching Chuan} and Lin, {Yee Shin}",
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Streptococcal pyrogenic exotoxin B inhibits apoptotic cell clearance by macrophages through protein S cleavage. / Chen, Chia Ling; Wu, Yueh Ying; Lin, Chiou Feng; Kuo, Chih Feng; Han, Chia Li; Wang, Shuying; Chuang, Woei Jer; Chen, Chiu Yueh; Wu, Jiunn Jong; Tsai, Pei Jane; Liu, Ching Chuan; Lin, Yee Shin.

In: Scientific reports, Vol. 6, 26026, 16.05.2016.

Research output: Contribution to journalArticle

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AU - Chen, Chia Ling

AU - Wu, Yueh Ying

AU - Lin, Chiou Feng

AU - Kuo, Chih Feng

AU - Han, Chia Li

AU - Wang, Shuying

AU - Chuang, Woei Jer

AU - Chen, Chiu Yueh

AU - Wu, Jiunn Jong

AU - Tsai, Pei Jane

AU - Liu, Ching Chuan

AU - Lin, Yee Shin

PY - 2016/5/16

Y1 - 2016/5/16

N2 - Clearance of apoptotic cells by macrophages plays an important role in maintaining tissue homeostasis. Previous study indicated that streptococcal pyrogenic exotoxin B (SPE B) reduces phagocytic activity in group A streptococcus (GAS) infection. Here, we demonstrate that SPE B causes an inhibitory effect on protein S-mediated phagocytosis. In the presence of SPE B, serum- and purified protein S-mediated phagocytosis of apoptotic cells were significantly inhibited. The binding abilities of protein S to apoptotic cells were decreased by treatment with SPE B. Bacterial culture supernatants from GAS NZ131 strain also caused a reduction of protein S binding to apoptotic cells, but speB mutant strain did not. SPE B directly cleaved protein S in vitro and in vivo, whereas a lower level of cleavage occurred in mice infected with a speB isogenic mutant strain. SPE B-mediated initial cleavage of protein S caused a disruption of phagocytosis, and also resulted in a loss of binding ability of protein S-associated C4b-binding protein to apoptotic cells. Taken together, these results suggest a novel pathogenic role of SPE B that initiates protein S degradation followed by the inhibition of apoptotic cell clearance by macrophages.

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