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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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Decreased macrophage phagocytosis in MBL- mice. Phagocytosis was assayed in vivo (a) and in vitro (b) as described in Materials and Methods. Phagocytosis is shown by mean fluorescence intensity for the ingested FITC-S. aureus. Bars indicate mean ± SE. **, P = 0.003; *, P = 0.009.
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fig7: Decreased macrophage phagocytosis in MBL- mice. Phagocytosis was assayed in vivo (a) and in vitro (b) as described in Materials and Methods. Phagocytosis is shown by mean fluorescence intensity for the ingested FITC-S. aureus. Bars indicate mean ± SE. **, P = 0.003; *, P = 0.009.

Mentions: In this study we observed that neutropenic MBL- mice are more susceptible to i.p. infection than neutropenic WT mice. CY-treated WT and MBL- mice, in addition to being neutropenic, had an 80% decrease in circulating monocytes and resident peritoneal macrophages, indicating that the effects of chemotherapy did not affect neutrophils alone. We reasoned that despite the reduction in the number, resident peritoneal macrophages, together with MBL, play a key role in restricting the early infection in the absence of neutrophils. We detected MBL in the peritoneal cavity of WT mice within hours of infection (unpublished data). Resident peritoneal macrophages were harvested 10 min after inoculation of FITC-S. aureus into the peritoneal cavity of WT and MBL- mice, and phagocytosis as bacterial uptake was analyzed by FACS®. There was a 40% reduction in bacterial phagocytosis by resident peritoneal macrophages from MBL- mice compared with those from WT mice (Fig. 7). In addition, the bacterial phagocytosis in vitro by peritoneal macrophages from WT mice was 35% less when FITC-S. aureus was opsonized with serum from MBL- mice compared with that from WT mice.


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)

Decreased macrophage phagocytosis in MBL- mice. Phagocytosis was assayed in vivo (a) and in vitro (b) as described in Materials and Methods. Phagocytosis is shown by mean fluorescence intensity for the ingested FITC-S. aureus. Bars indicate mean ± SE. **, P = 0.003; *, P = 0.009.
© Copyright Policy
Related In: Results  -  Collection

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

fig7: Decreased macrophage phagocytosis in MBL- mice. Phagocytosis was assayed in vivo (a) and in vitro (b) as described in Materials and Methods. Phagocytosis is shown by mean fluorescence intensity for the ingested FITC-S. aureus. Bars indicate mean ± SE. **, P = 0.003; *, P = 0.009.
Mentions: In this study we observed that neutropenic MBL- mice are more susceptible to i.p. infection than neutropenic WT mice. CY-treated WT and MBL- mice, in addition to being neutropenic, had an 80% decrease in circulating monocytes and resident peritoneal macrophages, indicating that the effects of chemotherapy did not affect neutrophils alone. We reasoned that despite the reduction in the number, resident peritoneal macrophages, together with MBL, play a key role in restricting the early infection in the absence of neutrophils. We detected MBL in the peritoneal cavity of WT mice within hours of infection (unpublished data). Resident peritoneal macrophages were harvested 10 min after inoculation of FITC-S. aureus into the peritoneal cavity of WT and MBL- mice, and phagocytosis as bacterial uptake was analyzed by FACS®. There was a 40% reduction in bacterial phagocytosis by resident peritoneal macrophages from MBL- mice compared with those from WT mice (Fig. 7). In addition, the bacterial phagocytosis in vitro by peritoneal macrophages from WT mice was 35% less when FITC-S. aureus was opsonized with serum from MBL- mice compared with that from WT mice.

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