Toll-Like Receptor 7 Triggers Immune Response to West Nile Virus

NEW YORK (Reuters Health) Feb 09 - Toll-like receptor 7 -- the mammalian host's first line of defense against West Nile virus infection - may represent a therapeutic target in the treatment of viral encephalitis, scientists report in the February 20 issue of Immunity, posted online on February 5.

Toll-like receptors (TLRs) are responsible for initiating innate immunity, lead author Dr. Terrence Town, from Cedars Sinai Medical Center in Los Angeles, explained in an interview with Reuters Health. Up to a dozen TLRs have been identified in mammals, each of which recognizes specific pathogens, such as bacteria, flagellated protozoans, and fungi. TLR3 mediates host recognition of viral components and intact West Nile virus.

"When we infected TLR3 knockout mice with West Nile virus, we expected the mice to do worse, and were surprised to see that they became more resistant," Dr. Town said.

They discovered that TLR3 activation elicits systemic TNF-alpha production, which increases permeability of the blood-brain barrier to the virus.

"Most individuals that receive a West Nile virus challenge by mosquito bite remain asymptomatic, and the body clears the virus, so we knew that other mechanisms must be in place that serve to clear this virus," the scientist continued.

Further work revealed that TLR7 also recognizes West Nile virus. TLR7 knockout mice were susceptible to lethal West Nile virus encephalitis, despite the upregulation of many proinflammatory cytokines in the peripheral circulation. However, levels of interleukin-23 were reduced, and homing of leukocytes, microglia, and macrophages to virus-infected cells in the brain was impaired.