Abstract
Severe infections with Streptococcus pyogenes, an important human pathogen, are associated with massive inflammatory reactions in the human host. Here we show that streptococcal M protein interacts with TLR2 on human peripheral blood monocytes. As a consequence, monocytes express the cytokines IL-6, IL-1beta, and TNF-alpha. This response is significantly increased in the presence of neutrophil-derived heparin-binding protein (HBP), which co-stimulates monocytes by interacting with CD11/CD18. Analysis of tissue biopsies from patients with necrotizing fasciitis revealed recruitment of neutrophils and monocytes to the infectious site, combined with the release of HBP. The results show that M protein, in synergy with HBP, evokes an inflammatory response that may contribute to the profound pathophysiological consequences seen in severe streptococcal infections.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Animals
- Antigens, Bacterial / metabolism
- Antigens, Bacterial / physiology*
- Antimicrobial Cationic Peptides
- Bacterial Outer Membrane Proteins / metabolism
- Bacterial Outer Membrane Proteins / physiology*
- Blood Proteins / metabolism
- Blood Proteins / physiology
- CD11 Antigens / physiology
- CD18 Antigens / physiology
- CHO Cells
- Carrier Proteins / metabolism
- Carrier Proteins / physiology*
- Cell Line
- Cricetinae
- Cytokines / metabolism
- Drug Synergism
- Humans
- Inflammation Mediators / metabolism
- Inflammation Mediators / physiology*
- Interleukin-6 / blood
- Interleukin-6 / metabolism
- Macrophages / metabolism
- Macrophages / microbiology
- Monocytes / metabolism
- Monocytes / microbiology
- Monocytes / pathology
- Neutrophils / metabolism
- Neutrophils / microbiology
- Signal Transduction / immunology
- Streptococcus pyogenes / immunology*
- Toll-Like Receptor 2 / metabolism
Substances
- AZU1 protein, human
- Antigens, Bacterial
- Antimicrobial Cationic Peptides
- Bacterial Outer Membrane Proteins
- Blood Proteins
- CD11 Antigens
- CD18 Antigens
- Carrier Proteins
- Cytokines
- Inflammation Mediators
- Interleukin-6
- TLR2 protein, human
- Toll-Like Receptor 2
- streptococcal M protein