期刊
JOURNAL OF INNATE IMMUNITY
卷 1, 期 3, 页码 202-214出版社
KARGER
DOI: 10.1159/000203645
关键词
Group A Streptococcus; Streptococcus pyogenes; Virulence factor; Innate immunity; M protein; Neutrophil; Mast cell; Extracellular traps; Antimicrobial peptide; Cathelicidin
类别
资金
- NIH [A1048694, A1077780, AR45676, A148176, A1071167]
- Wound Healing Foundation
- Deutsche Akademie der Naturforscher Leopoldina [BMBF-LPD 9901/8-187]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI052453, R21AI071167, R37AI052453, R01AI077780, R01AI048694, R21AI048176] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR045676] Funding Source: NIH RePORTER
M1 protein contributes to Group A Streptococcus (GAS) systemic virulence by interfering with phagocytosis and through proinflammatory activities when released from the cell surface. Here we identify a novel role of Mill protein in the stimulation of neutrophil and mast cell extracellular trap formation, yet also subsequent survival of the pathogen within these DNA-based innate defense structures. Targeted mutagenesis and heterologous expression studies demonstrate M1 protein promotes resistance to the human cathelicidin antimicrobial peptide LL-37, an important effector of bacterial killing within such phagocyte extracellular traps. Studies with purified recombinant protein fragments mapped the inhibition of cathelicidin killing to the M1 hypervariable N-terminal domain. A survey of GAS clinical isolates found that strains from patients with necrotizing fasciitis or toxic shock syndrome were significantly more likely to be resistant to cathelicidin than GAS M types not associated with invasive disease; M1 isolates were uniformly resistant. We conclude increased resistance to host cathelicidin and killing within phagocyte extracellular traps contribute to the propensity of M1 GAS strains to produce invasive infections. Copyright (C) 2009 S. Karger AG, Basel
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