Toll-like receptor (TLR) 2 and TLR9 expressed in trigeminal ganglia are critical to viral control during herpes simplex virus 1 infection.
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-γ and interleukin 1-β 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-γ, 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.
Lima
Graciela Kunrath
GK
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Laboratório de Imunopatologia, CPqRR/FIOCRUZ. Av. Augusto de Lima, 1715. CEP: 30.190-002 Belo Horizonte, MG, Brazil.
Zolini
Guilherme Pimenta
GP
Mansur
Daniel Santos
DS
Freire Lima
Bráulio Henrique
BH
Wischhoff
Uschi
U
Astigarraga
Ruiz Gerhardt
RG
Dias
Marcela França
MF
das Graças Almeida Silva
Mariana
M
Béla
Samantha Ribeiro
SR
do Valle Antonelli
Lis Ribeiro
LR
Arantes
Rosa Maria
RM
Gazzinelli
Ricardo Tostes
RT
Báfica
André
A
Kroon
Erna Geessien
EG
Campos
Marco Antônio
MA
D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D002460:Cell Line; D018925:Chemokines / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*; D012668:Trigeminal Ganglion / Q000276:immunology* / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha