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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 - May 16 2016

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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

ASJC Scopus subject areas

  • General

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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

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. / Streptococcal pyrogenic exotoxin B inhibits apoptotic cell clearance by macrophages through protein S cleavage. In: Scientific Reports. 2016 ; Vol. 6.
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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.",
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AU - Chen, Chiu Yueh

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AU - Tsai, Pei Jane

AU - Liu, Ching Chuan

AU - Lin, Yee Shin

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