title: Mannose-binding lectin-deficient mice are susceptible to infection with Staphylococcus aureus.
abstract: 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 wild-type 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.
authors.affiliation: Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, JRG 1402, Boston, MA 02114, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.forename: Joseph
authors.initials: J
authors.lastname: Dundee
authors.forename: Sarit
authors.initials: S
authors.lastname: Shahroor-Karni
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.forename: Jens Christian
authors.initials: JC
authors.lastname: Jensenius
authors.forename: Faten
authors.initials: F
authors.lastname: Gad
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
authors.forename: Kedarnath N
authors.initials: KN
authors.lastname: Sastry
authors.forename: R Alan B
authors.initials: RA
authors.lastname: Ezekowitz
mesh_terms: D000818:Animals; D004269:DNA, Bacterial / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D004198:Disease Susceptibility / Q000276:immunology; D008168:Lung / Q000382:microbiology; D037601:Mannose-Binding Lectin / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000382:microbiology; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology*
chemical_list: D004269:DNA, Bacterial; D037601:Mannose-Binding Lectin