Iron regulates the TLR4 inflammatory signaling pathway

Oct 05, 2009

Iron is a micronutrient essential to the survival of both humans and disease-causing microbes. Changes in iron levels therefore affect the severity of infectious diseases. For example, individuals with mutations in their HFE gene have exceedingly high levels of iron in their liver and are more susceptible to infection with a number of microbes.

Exactly how changes in iron levels affect susceptibility to infectious disease has not been clearly determined, although it has been observed that mice lacking Hfe mount an impaired following oral infection with the bacterium that causes salmonella.

Bobby Cherayil and colleagues, at Massachusetts General Hospital, Charlestown, have now defined a molecular mechanism underlying the impaired inflammatory response to oral infection with the bacterium that causes salmonella in mice lacking Hfe.

Specifically, these mice have low levels of free iron in known as macrophages and this impairs signaling along a pathway required for sensing the presence of bacteria such as the one that causes salmonella and triggering an inflammatory response (the TLR4/TRAM/TRIF pathway).

As drugs that mimic the altered iron distribution associated with Hfe deficiency reduced intestinal damage associated with infection with the salmonella-causing bacterium and reduced intestinal damage in a noninfectious inflammatory situation, the authors suggest that local manipulation of iron levels might provide a new approach to controlling inflammation.

More information: View this article at: www.jci.org/articles/view/3993… 4fae98a76d788644e09d

Source: Journal of Clinical Investigation

Explore further: Connection found between birth size and brain disorders

add to favorites email to friend print save as pdf

Related Stories

Europe's most common genetic disease is a liver disorder

Feb 06, 2008

Much less widely known than the dangerous consequences of iron deficiencies is the fact that too much iron can also cause problems. The exact origin of the genetic iron overload disorder hereditary hemochromatosis (HH) has ...

Salmonella in garden birds responsive to antibiotics

Jun 02, 2008

Scientists at the University of Liverpool have found that Salmonella bacteria found in garden birds are sensitive to antibiotics, suggesting that the infection is unlike the bacteria found in livestock and humans.

Iron and copper relationship is studied

Jul 24, 2007

U.S. scientists studying the relationship of iron and copper in the body have found when iron absorption by cells decreases, copper absorption increases.

Recommended for you

Connection found between birth size and brain disorders

3 hours ago

(Medical Xpress)—A trio of researchers has found what appears to be a clear connection between birth size and weight, and the two brain disorders, autism and schizophrenia. In their paper published in Proceedings of ...

A novel therapy for sepsis?

21 hours ago

A University of Tokyo research group has discovered that pentatraxin 3 (PTX3), a protein that helps the innate immune system target invaders such as bacteria and viruses, can reduce mortality of mice suffering ...

User comments : 0