Rare immune cell is asset and liability in fighting infection


In papers published online in Immunity, scientists at Washington University School of Medicine in St. Louis reveal that the cells, known as CD8 alpha+ dendritic cells (CD8a+ DCs), can help the body beat back infection by a common parasite, but the same cells can be hijacked by a bacterium to decimate the body’s defenses.

The trait that makes the cells both an asset and a liability is the way they alert other immune cells, causing them to attack invaders. CD8a+ DCs can sound the alarm in a manner that is particularly helpful for stripping away invaders’ disguises. But this process takes time, and Listeria bacteria can take advantage of that delay to wreak havoc inside the spleen.

“As we’ve discovered how useful these cells can be in fighting different kinds of infections, researchers have wondered why they’re so rare,” says Kenneth Murphy, MD, PhD, the Eugene L. Opie First Centennial Professor of Pathology and Immunology. “This may be why — overcommitting to any one defensive strategy opens up opportunities for counterstrategies that exploit it.”





In the second paper, Brian Edelson, MD, PhD, assistant professor of pathology and immunology, tested the cells against the bacteria Listeria, which can cause food poisoning. He discovered that CD8a+ DCs could make Listeria infection worse.

Listeria likes to get into immune cells using a pathway that typically leads to the bacteria’s death in garbage disposals inside the cell,” Murphy explains. “But that pathway is slowed down in CD8a+ DCs to ensure that they can retain part of the invader to display to other immune cells.”



“What we’re learning from basic studies, for example, has already enabled us to increase the number of CD8a+ DCs in mice until they’re about 30 to 40 percent of dendritic cells,” Murphy says. ”Learning more about how this cell interacts with other immune cells will allow us to create effective cancer vaccines.”

Mashayekhi M, Sandau MM, Dunay IR, Frickel EM, Khan A, Goldsmid RS, Sher A, PLoegh HL, Murphy TL, Sibley DL, Murphy KM. CD8a+ dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites. Immunity, Vol. 35, Issue 2.

Funding from the Howard Hughes Medical Institute, the American Heart Association and the National Institutes of Health supported this research.

Edelson BT, Bradstreet TR, Hildner K, Carrero JA, Frederick KE, Wumesh KC, Belizaire R, Aoshi T, Schreiber RD, Miller MJ, Murphy TL, Unanue ER, Murphy KM. CD8a+ dendritic cells are an obligate cellular entry point for productive infection by Listeria monocytogenes. Immunity, Volume 35, issue 2.

Funding from the Howard Hughes Medical Institute, the Burroughs Wellcome Fund Career Award for Medical Scientists, the Jack H. Ladenson Fellowship in Experimental Clinical Pathology at Washington University School of Medicine, the Emmy Noether Program of the German Research Foundation and the National Institutes of Health supported this research.
