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* Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, Lund, Sweden;
Institute for Microbiology and Hygiene, Charité University Medical Center, Humboldt University, Berlin, Germany;
Karolinska Institutet, Center for Infectious Medicine, Huddinge University Hospital, Stockholm, Sweden;
Medical Microbiology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, Malmö, Sweden; and
¶ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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-1
, and TNF-
. This response is significantly increased in the presence of neutrophil-derived heparin-binding protein (HBP), which costimulates 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.
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