Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 199, Issue 10, Pages 1379-1390Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20032207
Keywords
mannose-binding lectin; MBL; infection; neutropenia; innate immunity
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Funding
- NIAID NIH HHS [R01AI42788, R01 AI050875, R01 AI050875-01A2, R01 AI042788] Funding Source: Medline
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Gram-positive organisms like Staphylococcus aureus are a major cause of morbidity and mortality worldwide. Humoral response molecules together with phagocytes play a role in host responses to S. aureus. The mannose-binding lectin (MBL, also known as mannose-binding protein) is an oligomeric serum molecule that recognizes carbohydrates decorating a broad range of infectious agents including S. aureus. Circumstantial evidence in vitro and in vivo suggests that MBL plays a key role in first line host defense. We tested this contention directly in vivo by generating mice that were devoid of all MBL activity. We found that 100% of MBL-null mice died 48 h after exposure to an intravenous inoculation of S. aureus compared with 45% mortality in wildtype mice. Furthermore, we demonstrated that neutrophils and MBL are required to limit intraperitoneal infection with S. aureus. Our study provides direct evidence that MBL plays a key role in restricting the complications associated with S. aureus infection in mice and raises the idea that the MBL gene may act as a disease susceptibility gene against staphylococci infections in humans.
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