NutritionBacteria Are First Sensed By Cells Lining Blood Vessels, Not Immune Cells
Paul Kubes and colleagues, at the University of Calgary, Canada, have provided evidence in mice to refute the paradigm that the initial phase of the immune response to infection with Gram-negative bacteria (the recruitment of immune cells known as neutrophils to the site of infection) is triggered following immune sentinel-cell recognition of the bacterial molecule LPS via the protein TLR4. Rather, the researchers found that LPS recognition by TLR4 on the cells that line blood vessels (endothelial cells) is the crucial event that initiates neutrophil recruitment and bacterial clearance in mice.
In the study, mice engineered such that they expressed TLR4 exclusively on endothelial cells were found to be dramatically less susceptible to a lethal intraperitoneal dose of the bacterium E. coli than normal mice. This was because neutrophil recruitment to the site of infection was much more efficient in the engineered mice than in normal mice, as a result of many neutrophils being sequestered in the blood vessels of the lungs of normal mice. In contrast, TLR4 on endothelial cells was not involved in neutrophil recruitment following LPS administration into the airways, rather TLR4 on immune sentinel cells was the key trigger of neutrophil recruitment. The authors therefore conclude that TLR4 on endothelial and immune sentinel cells is crucial for infection with Gram-negative bacteria at different sites, the blood and tissues, and the lungs, respectively.
TITLE: Mice that exclusively express TLR4 on endothelial cells can efficiently clear a lethal systemic Gram-negative bacterial infection
AUTHOR:
Paul Kubes
University of Calgary, Calgary, Alberta, Canada.
View the PDF of this article at: https://www.the-jci.org/article.php?id=36411
Karen Honey
Journal of Clinical Investigation
JCI online early table of contents: June 15, 2009