RAGE: exacting a toll on the host in response to polymicrobial sepsis and Listeria monocytogenes.
The receptor for advanced glycation endproducts (RAGE) has complex roles in the immune/inflammatory response. RAGE is expressed on monocytes/macrophages, T and B lymphocytes, and dendritic cells. Previous studies illustrated that homozygous RAGE-/- mice subjected to overwhelming bacterial sepsis displayed normal clearance of pathogenic bacteria and significantly increased survival. In this issue of Critical Care, Lutterloh and colleagues confirm these findings and provide evidence that blocking antibodies to RAGE afford similar protection in mice, even when administration of anti-RAGE is delayed by 24 hours. Furthermore, these authors illustrate that deletion of RAGE is remarkably protective in mice infected with the intracellular pathogen Listeria monocytogenes. In this Commentary, we consider these findings and propose possible mechanisms by which RAGE exacts a heavy toll on the host in response to polymicrobial sepsis and L. monocytogenes.
Clynes
Raphael
R
Department of Medicine and Microbiology, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA.
Herold
Kevan
K
Schmidt
Ann Marie
AM
D000818:Animals; D006801:Humans; D008089:Listeria monocytogenes / Q000302:isolation & purification; D008088:Listeriosis / Q000378:metabolism* / Q000382:microbiology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018805:Sepsis / Q000378:metabolism* / Q000382:microbiology
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic