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Mannose-binding lectin-deficient mice are susceptible to infection with Staphylococcus aureus.

Shi L, Takahashi K, Dundee J, Shahroor-Karni S, Thiel S, Jensenius JC, Gad F, Hamblin MR, Sastry KN, Ezekowitz RA - J. Exp. Med. (2004)

Bottom Line: 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.Furthermore, we demonstrated that neutrophils and MBL are required to limit intraperitoneal infection with S. aureus.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, JRG 1402, Boston, MA 02114, USA.

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- 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.

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Increased mortality in MBL- mice from S. aureus infection. S. aureus was inoculated i.v. and survival was followed as described in Materials and Methods. Numbers of mice used were 15 WT, 14 MBL-, and 9 MBL- plus rhMBL. *, P < 0.0001.
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fig2: Increased mortality in MBL- mice from S. aureus infection. S. aureus was inoculated i.v. and survival was followed as described in Materials and Methods. Numbers of mice used were 15 WT, 14 MBL-, and 9 MBL- plus rhMBL. *, P < 0.0001.

Mentions: At 48 h the mortality was 100% for MBL- mice compared with 55% survival for WT mice (Fig. 2). Furthermore, pretreatment of MBL- mice with rhMBL partially rescued the phenotype in that the survival of MBL- mice was 45% by 48 h (Fig. 2). The phenotype of MBL-A KO and MBL-C KO mice was similar to that of WT mice (unpublished data). These results suggest that these two forms of MBL play a redundant role in resistance to S. aureus infection and that only when both proteins are absent the susceptibility to S. aureus is revealed.


Mannose-binding lectin-deficient mice are susceptible to infection with Staphylococcus aureus.

Shi L, Takahashi K, Dundee J, Shahroor-Karni S, Thiel S, Jensenius JC, Gad F, Hamblin MR, Sastry KN, Ezekowitz RA - J. Exp. Med. (2004)

Increased mortality in MBL- mice from S. aureus infection. S. aureus was inoculated i.v. and survival was followed as described in Materials and Methods. Numbers of mice used were 15 WT, 14 MBL-, and 9 MBL- plus rhMBL. *, P < 0.0001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211809&req=5

fig2: Increased mortality in MBL- mice from S. aureus infection. S. aureus was inoculated i.v. and survival was followed as described in Materials and Methods. Numbers of mice used were 15 WT, 14 MBL-, and 9 MBL- plus rhMBL. *, P < 0.0001.
Mentions: At 48 h the mortality was 100% for MBL- mice compared with 55% survival for WT mice (Fig. 2). Furthermore, pretreatment of MBL- mice with rhMBL partially rescued the phenotype in that the survival of MBL- mice was 45% by 48 h (Fig. 2). The phenotype of MBL-A KO and MBL-C KO mice was similar to that of WT mice (unpublished data). These results suggest that these two forms of MBL play a redundant role in resistance to S. aureus infection and that only when both proteins are absent the susceptibility to S. aureus is revealed.

Bottom Line: 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.Furthermore, we demonstrated that neutrophils and MBL are required to limit intraperitoneal infection with S. aureus.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, JRG 1402, Boston, MA 02114, USA.

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- 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.

Show MeSH
Related in: MedlinePlus