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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 bacterial loads in blood and organs of MBL- mice. Bacterial titers were assayed at 24 h after i.v. inoculation of S. aureus as described in Materials and Methods. Six mice were in each group. Open bars, WT; closed bars, MBL-. Bars indicate mean ± SD. *, P ≤ 0.05; **, P < 0.01.
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fig3: Increased bacterial loads in blood and organs of MBL- mice. Bacterial titers were assayed at 24 h after i.v. inoculation of S. aureus as described in Materials and Methods. Six mice were in each group. Open bars, WT; closed bars, MBL-. Bars indicate mean ± SD. *, P ≤ 0.05; **, P < 0.01.

Mentions: Next, we investigated whether the enhanced susceptibility of MBL- mice to S. aureus infection was a result of altered distribution and growth of the bacteria in the blood, kidney, spleen, liver, and lung. One and a half logs more CFU/ml was found in the blood of MBL- mice compared with WT mice at 24 h after inoculation (Fig. 3). It was not possible to examine the later kinetics of bacteremia in MBL- mice as all had died by 48 h, but longer studies in WT mice that survived the infection indicated that these mice sterilize the blood several days after inoculation (not depicted). There were statistically significant higher bacterial loads in the kidney, spleen, and liver in MBL- mice compared with WT mice at 24 h after inoculation (Fig. 3).


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 bacterial loads in blood and organs of MBL- mice. Bacterial titers were assayed at 24 h after i.v. inoculation of S. aureus as described in Materials and Methods. Six mice were in each group. Open bars, WT; closed bars, MBL-. Bars indicate mean ± SD. *, P ≤ 0.05; **, P < 0.01.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Increased bacterial loads in blood and organs of MBL- mice. Bacterial titers were assayed at 24 h after i.v. inoculation of S. aureus as described in Materials and Methods. Six mice were in each group. Open bars, WT; closed bars, MBL-. Bars indicate mean ± SD. *, P ≤ 0.05; **, P < 0.01.
Mentions: Next, we investigated whether the enhanced susceptibility of MBL- mice to S. aureus infection was a result of altered distribution and growth of the bacteria in the blood, kidney, spleen, liver, and lung. One and a half logs more CFU/ml was found in the blood of MBL- mice compared with WT mice at 24 h after inoculation (Fig. 3). It was not possible to examine the later kinetics of bacteremia in MBL- mice as all had died by 48 h, but longer studies in WT mice that survived the infection indicated that these mice sterilize the blood several days after inoculation (not depicted). There were statistically significant higher bacterial loads in the kidney, spleen, and liver in MBL- mice compared with WT mice at 24 h after inoculation (Fig. 3).

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