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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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Cytokine production after S. aureus infection. Levels of cytokine induction was less at 2 h but more at 24 h in MBL- mice compared with WT mice after S. aureus i.v. inoculation. Six mice were used in each group. Bars indicate mean ± SE. *, P < 0.05; **, P < 0.001.
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fig5: Cytokine production after S. aureus infection. Levels of cytokine induction was less at 2 h but more at 24 h in MBL- mice compared with WT mice after S. aureus i.v. inoculation. Six mice were used in each group. Bars indicate mean ± SE. *, P < 0.05; **, P < 0.001.

Mentions: The levels of TNF-α and IL-6 in the blood of MBL- and WT mice were determined at 2 and 24 h after the i.v. inoculation. Both TNF-α and IL-6 (P < 0.0001) were reduced in the serum of MBL- mice compared with WT mice at 2 h (Fig. 5). In contrast, at 24 h there was a 15-fold increase in TNF-α (P < 0.05) and an eightfold increase in IL-6 (P < 0.0005) in the serum of MBL- mice compared with WT mice (Fig. 5). Preliminary in vitro studies with bone marrow–derived macrophages from MBL- mice that were cultured with heat-killed S. aureus showed enhancement of IL-6 secretion at 24 h. A similar trend was also observed for TNF-α secretion (unpublished data).


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)

Cytokine production after S. aureus infection. Levels of cytokine induction was less at 2 h but more at 24 h in MBL- mice compared with WT mice after S. aureus i.v. inoculation. Six mice were used in each group. Bars indicate mean ± SE. *, P < 0.05; **, P < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Cytokine production after S. aureus infection. Levels of cytokine induction was less at 2 h but more at 24 h in MBL- mice compared with WT mice after S. aureus i.v. inoculation. Six mice were used in each group. Bars indicate mean ± SE. *, P < 0.05; **, P < 0.001.
Mentions: The levels of TNF-α and IL-6 in the blood of MBL- and WT mice were determined at 2 and 24 h after the i.v. inoculation. Both TNF-α and IL-6 (P < 0.0001) were reduced in the serum of MBL- mice compared with WT mice at 2 h (Fig. 5). In contrast, at 24 h there was a 15-fold increase in TNF-α (P < 0.05) and an eightfold increase in IL-6 (P < 0.0005) in the serum of MBL- mice compared with WT mice (Fig. 5). Preliminary in vitro studies with bone marrow–derived macrophages from MBL- mice that were cultured with heat-killed S. aureus showed enhancement of IL-6 secretion at 24 h. A similar trend was also observed for TNF-α secretion (unpublished data).

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