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.
authors.affiliation: Translational Research Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yueh-Ying
authors.initials: YY
authors.lastname: Wu
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
authors.affiliation: Department of Nursing, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Chih-Feng
authors.initials: CF
authors.lastname: Kuo
authors.affiliation: Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Li
authors.initials: CL
authors.lastname: Han
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shuying
authors.initials: S
authors.lastname: Wang
authors.affiliation: Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.|Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Woei-Jer
authors.initials: WJ
authors.lastname: Chuang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chiu-Yueh
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.|Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jiunn-Jong
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.|Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Pei-Jane
authors.initials: PJ
authors.lastname: Tsai
authors.affiliation: Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.|Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis; D050716:Complement C4b-Binding Protein / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D010587:Phagocytosis; D011485:Protein Binding; D017293:Protein S / Q000378:metabolism*; D059748:Proteolysis; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000502:physiology*; D000074084:THP-1 Cells
chemical_list: D050716:Complement C4b-Binding Protein; D017293:Protein S; D003546:Cysteine Endopeptidases; C042477:streptopain