PMID- 20864677 OWN - NLM STAT- MEDLINE DCOM- 20110321 LR - 20211020 IS - 1525-2191 (Electronic) IS - 0002-9440 (Print) IS - 0002-9440 (Linking) VI - 177 IP - 5 DP - 2010 Nov TI - Toll-like receptor (TLR) 2 and TLR9 expressed in trigeminal ganglia are critical to viral control during herpes simplex virus 1 infection. PG - 2433-45 LID - 10.2353/ajpath.2010.100121 [doi] AB - 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 responses in the TG, which prevent HSV-1 encephalitis. FAU - Lima, Graciela Kunrath AU - Lima GK AD - Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Laboratorio de Imunopatologia, CPqRR/FIOCRUZ. Av. Augusto de Lima, 1715. CEP: 30.190-002 Belo Horizonte, MG, Brazil. FAU - Zolini, Guilherme Pimenta AU - Zolini GP FAU - Mansur, Daniel Santos AU - Mansur DS FAU - Freire Lima, Braulio Henrique AU - Freire Lima BH FAU - Wischhoff, Uschi AU - Wischhoff U FAU - Astigarraga, Ruiz Gerhardt AU - Astigarraga RG FAU - Dias, Marcela Franca AU - Dias MF FAU - das Gracas Almeida Silva, Mariana AU - das Gracas Almeida Silva M FAU - Bela, Samantha Ribeiro AU - Bela SR FAU - do Valle Antonelli, Lis Ribeiro AU - do Valle Antonelli LR FAU - Arantes, Rosa Maria AU - Arantes RM FAU - Gazzinelli, Ricardo Tostes AU - Gazzinelli RT FAU - Bafica, Andre AU - Bafica A FAU - Kroon, Erna Geessien AU - Kroon EG FAU - Campos, Marco Antonio AU - Campos MA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100923 PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (Interleukin-12 Subunit p40) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 9) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Brain/immunology/pathology/virology MH - Cell Line MH - Chemokines/blood/immunology MH - Cytokines/blood/immunology MH - Herpes Simplex/*immunology/*virology MH - Herpesvirus 1, Human/*immunology/pathogenicity MH - Humans MH - Interleukin-12 Subunit p40/immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Toll-Like Receptor 2/genetics/*immunology MH - Toll-Like Receptor 9/genetics/*immunology MH - Trigeminal Ganglion/*immunology/*virology MH - Tumor Necrosis Factor-alpha/immunology PMC - PMC2966801 EDAT- 2010/09/25 06:00 MHDA- 2011/03/22 06:00 PMCR- 2011/11/01 CRDT- 2010/09/25 06:00 PHST- 2010/09/25 06:00 [entrez] PHST- 2010/09/25 06:00 [pubmed] PHST- 2011/03/22 06:00 [medline] PHST- 2011/11/01 00:00 [pmc-release] AID - S0002-9440(10)60295-7 [pii] AID - 10.2353/ajpath.2010.100121 [doi] PST - ppublish SO - Am J Pathol. 2010 Nov;177(5):2433-45. doi: 10.2353/ajpath.2010.100121. Epub 2010 Sep 23.