Finding Has Implications for Treating Herpes
Yale School of Medicine researchers have determined how the body’s immune system springs into action when invaded by the herpes simplex virus, which can lead to fatal sporadic encephalitis in infants and children.
In a study published this month in the Proceedings of the National Academy of Sciences, the researchers found only a handful of patients carry a form of the herpes simplex virus type 1 (HSV-1) that activates Toll-like receptor 2 (TLR2), one of two key immune receptors. In contrast, all forms of HSV-1 viruses isolated from patients activated Toll-like receptor 9 (TLR9).
There were no distinguishing symptoms among patients with the rare form, although the sample size was too small to draw any statistical conclusions, according to senior author Akiko Iwasaki, associate professor of immunobiology.
“What was interesting was the observation that for the HSV-1 variant that triggered TLR2, full activation of dendritic cells also required TLR9, suggesting that there is a sequential activation of these two receptors within the same dendritic cell,” Iwasaki said.
Dendritic cells are immune cells that are present in small quantities in tissues that are in contact with the external environment, mainly the skin and the inner lining of the nose, lungs, stomach and intestines. Once activated, they migrate to the lymphoid tissues where they interact with T cells and B cells to initiate and shape the immune response.
Iwasaki said the researchers also found that all forms of HSV-1 that they tested triggered TLR-9 in a specialized cell known as the plasmacytoid dendritic cell. Plasmacytoid dendritic cells act as factories for type 1 interferons, which have potent antiviral activities against many types of viruses.
“This study has implications on the possible treatment options for herpes encephalitis by controlling inflammatory pathways induced through these Toll-like receptors,” she said.
Co-authors included Ayuko Sato, postdoctoral fellow, and Melissa Linehan, research associate.
PNAS 103: 17343-17948 (November 3, 2006)