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Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice
A Haziot1, E Ferrero, F Köntgen
1Division of Molecular Medicine, North Shore University Hospital, Cornell University Medical College, Manhasset, New York 11030, USA.
Abstract:
Endotoxin shock is the result of activation of the immune system by endotoxin/LPS, a component of Gram-negative bacteria. CD14, a GPI-anchored glycoprotein expressed strongly by monocyte/macrophages, is one of several receptors for endotoxin/LPS. The role of CD14 in bacterial-induced and LPS-induced shock was tested in CD14-deficient mice produced by gene targeting in embryonic stem cells. CD14-deficient mice were found to be highly resistant to shock induced by either live Gram-negative bacteria or LPS; however, at very high concentrations of LPS or bacteria, responses through non-CD14 receptors could be detected. Surprisingly, CD14-deficient mice also showed dramatically reduced levels of bacteremia, suggesting an unexpected role for CD14 in the dissemination of Gram-negative bacteria.
Insights
Mice lacking CD14 showed significant resistance to endotoxin shock and reduced bacterial spread. This highlights CD14's crucial role in immune response and bacterial dissemination.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Endotoxin shock arises from immune system activation by Gram-negative bacteria components.
- CD14, a monocyte/macrophage receptor, is a key player in endotoxin recognition.
Purpose of the Study:
- To investigate the role of CD14 in endotoxin/LPS-induced shock.
- To determine CD14's function in Gram-negative bacterial infections.
Main Methods:
- Generation of CD14-deficient mice using gene targeting in embryonic stem cells.
- Testing resistance to shock induced by live Gram-negative bacteria and LPS.
- Quantification of bacteremia levels in wild-type and CD14-deficient mice.
Main Results:
- CD14-deficient mice exhibited high resistance to shock from both live bacteria and LPS.
- Responses via non-CD14 receptors were observed at very high endotoxin or bacterial concentrations.
- A surprising, significant reduction in bacteremia was noted in CD14-deficient mice.
Conclusions:
- CD14 is essential for mediating endotoxin shock.
- CD14 plays an unexpected role in the dissemination of Gram-negative bacteria.
- Targeting CD14 may offer therapeutic strategies for sepsis and bacterial infections.