Streptococcal M protein: a multipotent and powerful inducer of inflammation.
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.
Påhlman
Lisa I
LI
Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Biomedicinskt Centrum B14, Lund University, Tornavägen 10, SE-221 84 Lund, Sweden.
Mörgelin
Matthias
M
Eckert
Jana
J
Johansson
Linda
L
Russell
Wayne
W
Riesbeck
Kristian
K
Soehnlein
Oliver
O
Lindbom
Lennart
L
Norrby-Teglund
Anna
A
Schumann
Ralf R
RR
Björck
Lars
L
Herwald
Heiko
H
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism / Q000502:physiology*; D023181:Antimicrobial Cationic Peptides; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism / Q000502:physiology; D018845:CD11 Antigens / Q000502:physiology; D018821:CD18 Antigens / Q000502:physiology; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism
C062991:AZU1 protein, human; D000942:Antigens, Bacterial; D023181:Antimicrobial Cationic Peptides; D001425:Bacterial Outer Membrane Proteins; D001798:Blood Proteins; D018845:CD11 Antigens; D018821:CD18 Antigens; D002352:Carrier Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C014689:streptococcal M protein