PMID- 24479442
OWN - NLM
STAT- MEDLINE
DCOM- 20140916
LR  - 20211021
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 11
DP  - 2014 Jan 30
TI  - Defense against HSV-1 in a murine model is mediated by iNOS and orchestrated by 
      the activation of TLR2 and TLR9 in trigeminal ganglia.
PG  - 20
LID - 10.1186/1742-2094-11-20 [doi]
AB  - BACKGROUND: Herpes simplex 1 (HSV-1) causes various human clinical 
      manifestations, ranging from simple cold sores to encephalitis. Innate immune 
      cells recognize pathogens through Toll-like receptors (TLRs), thus initiating the 
      immune response. Previously, we demonstrated that the immune response against 
      HSV-1 is dependent on TLR2 and TLR9 expression and on IFN gamma production in the 
      trigeminal ganglia (TG) of infected mice. In this work, we further investigated 
      the cells, molecules, and mechanisms of HSV-1 infection control, especially those 
      that are TLR-dependent. METHODS: C57BL/6 wild-type (WT), TLR2-/-, TLR9-/-, and 
      TLR2/9-/- mice were intranasally infected with HSV-1. On the viral peak day, the 
      TG and brains were collected from mice and TLR expression was measured in the TG 
      and brain and inducible nitric oxide synthase (iNOS) expression was measured in 
      the TG by real-time PCR. Immunofluorescence assays were performed in mice TG to 
      detect iNOS production by F4/80+ cells. Intraperitoneal macrophages nitric oxide 
      (NO) production was evaluated by the Griess assay. WT, CD8-/-, RAG-/-, and 
      iNOS-/- mice were intranasally infected in a survival assay, and their cytokine 
      expression was measured in the TG by real-time PCR. RESULTS: Infected WT mice 
      exhibited significantly increased TLR expression, compared with their respective 
      controls, in the TG but not in the brain. TLR-deficient mice had moderately 
      increased TLR expression in the TG and brain in compare with the non-infected 
      animals. iNOS expression in the WT infected mice TG was higher than in the other 
      groups with increased production by macrophages in the WT infected mice, which 
      did not occur in the TLR2/9-/- mice. Additionally, the intraperitoneal 
      macrophages of the WT mice had a higher production of NO compared with those of 
      the TLR-deficient mice. The CD8-/-, RAG-/-, and iNOS-/- mice had 100% mortality 
      after the HSV-1 infection compared with 10% of the WT mice. Cytokines were 
      overexpressed in the iNOS-/- infected mice, while the RAG-/- mice were nearly 
      unresponsive to the virus. CONCLUSION: TLRs efficiently orchestrate the innate 
      immune cells, eliciting macrophage response (with NO production by the 
      macrophages), thereby controlling the HSV-1 infection through the immune response 
      in the TG of mice.
FAU - Zolini, Guilherme Pimenta
AU  - Zolini GP
FAU - Lima, Graciela Kunrath
AU  - Lima GK
FAU - Lucinda, Natalia
AU  - Lucinda N
FAU - Silva, Mariana Almeida
AU  - Silva MA
FAU - Dias, Marcela Franca
AU  - Dias MF
FAU - Pessoa, Natalia Lima
AU  - Pessoa NL
FAU - Coura, Bruna Pizziolo
AU  - Coura BP
FAU - Cartelle, Christiane Teixeira
AU  - Cartelle CT
FAU - Arantes, Rosa Maria Esteves
AU  - Arantes RM
FAU - Kroon, Erna Geessien
AU  - Kroon EG
FAU - Campos, Marco Antonio
AU  - Campos MA
AD  - Laboratorio de Imunopatologia, Imunologia de Doencas Virais, Centro de Pesquisas 
      Rene Rachou, Fundacao Oswaldo Cruz, Fiocruz, Av, Augusto de Lima 1715, Belo 
      Horizonte, Minas Gerais 30190-002, Brazil. marcoasc@cpqrr.fiocruz.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140130
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Cytokines)
RN  - 0 (Hepatitis B Core Antigens)
RN  - 0 (Pirb protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Thioglycolates)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 9)
RN  - 0 (Viral Core Proteins)
RN  - 0 (p22 core protein, hepatitis B virus)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Animals
MH  - Brain/metabolism/pathology/virology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Hepatitis B Core Antigens/metabolism
MH  - Herpes Simplex/*pathology
MH  - Herpesvirus 1, Human/*physiology
MH  - Humans
MH  - Lymphocytes/drug effects/virology
MH  - Macrophages/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nitric Oxide Synthase Type II/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, Immunologic/metabolism
MH  - Thioglycolates/therapeutic use
MH  - Toll-Like Receptor 2/genetics/*metabolism
MH  - Toll-Like Receptor 9/genetics/*metabolism
MH  - Trigeminal Ganglion/*metabolism
MH  - Viral Core Proteins/metabolism
PMC - PMC3922087
EDAT- 2014/02/01 06:00
MHDA- 2014/09/17 06:00
PMCR- 2014/01/30
CRDT- 2014/02/01 06:00
PHST- 2013/06/17 00:00 [received]
PHST- 2014/01/14 00:00 [accepted]
PHST- 2014/02/01 06:00 [entrez]
PHST- 2014/02/01 06:00 [pubmed]
PHST- 2014/09/17 06:00 [medline]
PHST- 2014/01/30 00:00 [pmc-release]
AID - 1742-2094-11-20 [pii]
AID - 10.1186/1742-2094-11-20 [doi]
PST - epublish
SO  - J Neuroinflammation. 2014 Jan 30;11:20. doi: 10.1186/1742-2094-11-20.