Histidine-rich glycoprotein promotes bacterial entrapment in clots and decreases mortality in a mouse model of sepsis.
Streptococcus pyogenes is a significant bacterial pathogen in humans. In this study, histidine-rich glycoprotein (HRG), an abundant plasma protein, was found to kill S pyogenes. Furthermore, S pyogenes grew more efficiently in HRG-deficient plasma, and clots formed in this plasma were significantly less effective at bacterial entrapment and killing. HRG-deficient mice were strikingly more susceptible to S pyogenes infection. These animals failed to control the infection at the local subcutaneous site, and abscess formation and inflammation were diminished compared with control animals. As a result, bacterial dissemination occurred more rapidly in HRG-deficient mice, and they died earlier and with a significantly higher mortality rate than control animals. HRG-deficient mice supplemented with purified HRG gave the same phenotype as control animals, demonstrating that the lack of HRG was responsible for the increased susceptibility. The results demonstrate a previously unappreciated role for HRG as a regulator of inflammation and in the defense at the local site of bacterial infection.
Shannon
Oonagh
O
Divisions of Infection Medicine, University, Lund, Sweden
Rydengård
Victoria
V
Schmidtchen
Artur
A
Mörgelin
Matthias
M
Alm
Per
P
Sørensen
Ole E
OE
Björck
Lars
L
D000818:Animals; D001777:Blood Coagulation / Q000235:genetics / Q000502:physiology; D001798:Blood Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D018805:Sepsis / Q000097:blood* / Q000276:immunology / Q000382:microbiology*; D013290:Streptococcal Infections / Q000097:blood* / Q000276:immunology / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D000099053:Histidine-Rich Glycoprotein
D001798:Blood Proteins; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein