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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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Restricted bacterial growth in blood of WT mice and enhanced growth in blood but not in plasma of MBL- mice. Open bars, at 10 min; closed bars, at 2 h. (a) Bacterial growth in plasma. Results are shown as a percentage of bacterial growth in WT plasma at 10 min. Pooled plasma was used and the assay was performed in triplicates as described in Materials and Methods. Bars indicate mean ± SD. (b) Results are shown as a percentage of bacterial growth in WT blood at 10 min. Blood was collected from four mice individually and the assay was performed in triplicates as described in Materials and Methods. Bars indicate mean ± SD. *, P < 0.05
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fig4: Restricted bacterial growth in blood of WT mice and enhanced growth in blood but not in plasma of MBL- mice. Open bars, at 10 min; closed bars, at 2 h. (a) Bacterial growth in plasma. Results are shown as a percentage of bacterial growth in WT plasma at 10 min. Pooled plasma was used and the assay was performed in triplicates as described in Materials and Methods. Bars indicate mean ± SD. (b) Results are shown as a percentage of bacterial growth in WT blood at 10 min. Blood was collected from four mice individually and the assay was performed in triplicates as described in Materials and Methods. Bars indicate mean ± SD. *, P < 0.05

Mentions: To evaluate the relative contribution of direct complement-mediated lysis and MBL-dependent opsonophagocytosis, we incubated S. aureus in plasma and serum of WT, MBL-, and C3- mice. We found that none of the plasma (Fig. 4 a) and sera (not depicted) restricted the growth of bacteria at 10 min or 2 h after inoculation. In addition, there was no difference in the growth rate at all three conditions (Fig. 4 a). By contrast, ex vivo whole blood killing assay revealed that after 2 h of incubation the growth of S. aureus was restricted in whole blood from WT mice compared with 10 min of incubation, whereas S. aureus continued to grow in whole blood from MBL- mice (Fig. 4 b). These results indicate that phagocytes, MBL, and complement are required for S. aureus killing.


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)

Restricted bacterial growth in blood of WT mice and enhanced growth in blood but not in plasma of MBL- mice. Open bars, at 10 min; closed bars, at 2 h. (a) Bacterial growth in plasma. Results are shown as a percentage of bacterial growth in WT plasma at 10 min. Pooled plasma was used and the assay was performed in triplicates as described in Materials and Methods. Bars indicate mean ± SD. (b) Results are shown as a percentage of bacterial growth in WT blood at 10 min. Blood was collected from four mice individually and the assay was performed in triplicates as described in Materials and Methods. Bars indicate mean ± SD. *, P < 0.05
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Restricted bacterial growth in blood of WT mice and enhanced growth in blood but not in plasma of MBL- mice. Open bars, at 10 min; closed bars, at 2 h. (a) Bacterial growth in plasma. Results are shown as a percentage of bacterial growth in WT plasma at 10 min. Pooled plasma was used and the assay was performed in triplicates as described in Materials and Methods. Bars indicate mean ± SD. (b) Results are shown as a percentage of bacterial growth in WT blood at 10 min. Blood was collected from four mice individually and the assay was performed in triplicates as described in Materials and Methods. Bars indicate mean ± SD. *, P < 0.05
Mentions: To evaluate the relative contribution of direct complement-mediated lysis and MBL-dependent opsonophagocytosis, we incubated S. aureus in plasma and serum of WT, MBL-, and C3- mice. We found that none of the plasma (Fig. 4 a) and sera (not depicted) restricted the growth of bacteria at 10 min or 2 h after inoculation. In addition, there was no difference in the growth rate at all three conditions (Fig. 4 a). By contrast, ex vivo whole blood killing assay revealed that after 2 h of incubation the growth of S. aureus was restricted in whole blood from WT mice compared with 10 min of incubation, whereas S. aureus continued to grow in whole blood from MBL- mice (Fig. 4 b). These results indicate that phagocytes, MBL, and complement are required for S. aureus killing.

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