Toll-Like Receptor (TLR) 2 and TLR9 Expressed in Trigeminal Ganglia are Critical to Viral Control During Herpes Simplex Virus 1 Infection

作者：Lima Graciela Kunrath; Zolini Guilherme Pimenta; Mansur Daniel Santos; Freire Lima Braulio Henrique; Wischhoff Uschi; Astigarraga Ruiz Gerhardt; Dias Marcela Franca; Almeida Silva Mariana das Graces; Bela Samantha Ribeiro; do Valle Antonelli Lis Ribeiro; Arantes Rosa Maria; Gazzinelli Ricardo Tostes; Bafica Andre; Kroon Erna Geessien; Campos Marco Antonio^*

来源：American Journal Of Pathology, 2010, 177(5): 2433-2445.

DOI：10.2353/ajpath.2010.100121

Herpes simplex virus 1 (HSV-1) is a neurotropic DNA virus that is responsible for several clinical manifestations in humans, including encephalitis. HSV-1 triggers toll-like receptors (TLRs), which elicit cytokine production. Viral multiplication and cytokine expression in C57BL/6 wild-type (WT) mice infected with HSV-1 were evaluated. Virus was found in the trigeminal ganglia (TG), but not in the brains of animals without signs of encephalitis, between 2 and 6 days postinfection (d.p.i.). Cytokine expression in the TG peaked at 5 d.p.i. TLR9(-/-) and TLR2/9(-/-) mice were more susceptible to the virus, with 60% and 100% mortality, respectively, as opposed to 10% in the WT and TLR2(-/-) mice. Increased levels of both CXCL10/IP-10 and CCL2/MCP-1, as well as reduced levels of interferon-gamma and interleukin 1-beta transcripts, measured in both the TG and brains at 5 d.p.i., and the presence of virus in the brain were correlated with total mortality in TLR2/9(-/-) mice. Cytokine alterations in TLR2/9(-/-) mice coincided with histopathological changes in their brains, which did not occur in WT and TLR2(-/-) mice and occurred only slightly in TLR9(-/-) mouse brain. Increased cellularity, macrophages, CD8 T cells producing interferon-gamma, and expression levels of TLR2 and TLR9 were detected in the TG of WT-infected mice. We hypothesize that HSV-1 infection is controlled by TLR-dependent immune response; in the TG, which prevent HSV-1 encephalitis. (Am J Pathol 2010, 177:2433-2445; DOI: 10.2353/ajpath.2010.100121)

• 出版日期2010-11