Toll-like receptor (TLR) 2 and TLR9 expressed in trigeminal ganglia are critical to viral control during herpes simplex virus 1 infection

Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil / University of Massachusetts Medical School. Worcester, MA, USA.
Universidade Federal de Santa Catarina. Laboratorio de Imunologia e Doenças Infecciosas. Florianópolis, SC, Brazil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.

Abstract

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.

Keywords

Chemokines/immunology
Herpesvirus 1
Human/immunology
Interleukin-12 Subunit p40/immunology
Tumor Necrosis Factor-alpha/immunology

Publisher

American Society for Investigative Pathology

Citation

LIMA, Graciela Kunrath e al. Toll-like receptor (TLR) 2 and TLR9 expressed in trigeminal ganglia are critical to viral control during herpes simplex virus 1 infection. The American Journal of Pathology, v. 177, n. 5, p. 2433-2445, Nov. 2010.

DOI

10.2353/ajpath.2010.100121

ISSN

0002-9440

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/6921

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