Bacterial pathogenesis: Haem, sweet haem

Abstract

A new report in Nature Medicine has revealed that recognition of West Nile virus (WNV) by Toll-like receptor 3 (Tlr3) is the major factor allowing this virus to cross the blood–brain barrier (BBB) and cause lethal encephalitis. WNV is a single-stranded RNA (ssRNA) flavivirus with a life cycle that primarily involves birds and mosquitoes; however, humans and horses can also become infected. In humans, infection is generally asymptomatic, and if West Nile fever does develop then the illness is generally mild and self-limiting. In elderly and immunocompromised individuals, however,WNV infection can progress to severe neurological disease. The molecular details of the pathogenesis of severe disease are scarce. It is known that some TLRs can detect viral motifs such as ssRNA. In this study, researchers investigated the role of one of these TLRs, Tlr3, in the detection of WNV using a mouse model of WNV encephalitis. Initial investigations showed that following intraperitoneal challenge with a lethal dose of WNV, Tlr3 mice were more resistant to infection than wild-type mice. Quantitative PCR assays showed that, following this challenge, the viral burden in the periphery (blood and spleen) was increased in Tlr3 mice compared with wild-type mice. Analysis of blood cytokine levels showed increased levels of inflammatory cytokines in wild-type, compared with Tlr3, mice early in infection. The analysis was then switched from the periphery to the brain. A comparison of the viral load in brain tissue found that in Tlr3 mice the levels of WNV RNA were significantly lower compared with wild-type mice at day 6 after infection. The inflammatory cytokine profiles indicated that the inflammatory reaction was markedly reduced in Tlr3 mice and immunofluorescence work showed that the numbers of activated microglia (brain macrophages) and infiltrating leukocytes were reduced in Tlr3 mice, indicating fewer neuropathological effects. Collectively, these results strongly indicated that Tlr3 did have a role in

DOI: 10.1038/nrmicro1076

Cite this paper

@article{OConnell2005BacterialPH, title={Bacterial pathogenesis: Haem, sweet haem}, author={David O'Connell}, journal={Nature Reviews Microbiology}, year={2005}, volume={3}, pages={4-4} }