Dual TLR2/9 Recognition of Herpes Simplex Virus Infection Is Required for Recruitment and Activation of Monocytes and NK Cells and Restriction of Viral Dissemination to the Central Nervous System

Frontiers in Immunology
Erdenebileg UyangaaSeong Kug Eo

Abstract

The importance of TLR2 and TLR9 in the recognition of infection with herpes simplex virus (HSV) and HSV-caused diseases has been described, but some discrepancies remain concerning the benefits of these responses. Moreover, the impact of TLR2/9 on innate and adaptive immune responses within relevant mucosal tissues has not been elucidated using natural mucosal infection model of HSV. Here, we demonstrate that dual TLR2/9 recognition is essential to provide resistance against mucosal infection with HSV via an intravaginal route. Dual TLR2/9 ablation resulted in the highly enhanced mortality with exacerbated symptoms of encephalitis compared with TLR2 or TLR9 deficiency alone, coinciding with highly increased viral load in central nervous system tissues. TLR2 appeared to play a minor role in providing resistance against mucosal infection with HSV, since TLR2-ablated mice showed higher survival rate compared with TLR9-ablated mice. Also, the high mortality in dual TLR2/9-ablated mice was closely associated with the reduction in early monocyte and NK cell infiltration in the vaginal tract (VT), which was likely to correlate with low expression of cytokines and CCR2 ligands (CCL2 and CCL7). More interestingly, our data revealed that...Continue Reading

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Citations

Oct 2, 2020·Microbiology and Molecular Biology Reviews : MMBR·Huifang Zhu, Chunfu Zheng
Jul 28, 2020·International Journal of Molecular Sciences·Kevin DanastasAnthony L Cunningham
Dec 19, 2019·Frontiers in Microbiology·Yingying Lin, Chunfu Zheng
May 23, 2019·Frontiers in Cellular and Infection Microbiology·Eduardo I TognarelliPablo A González
Oct 30, 2020·Cells·Nina D AnfinogenovaDmitriy N Atochin
Feb 25, 2020·Cellular Immunology·Ferdaus Mohd Altaf HossainSeong Kug Eo
Jul 24, 2021·Expert Review of Vaccines·Vindya Nilakshi WijesingheSunil Kumar Lal
Oct 9, 2021·Clinical Science·Laura MarongiuFrancesca Granucci

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Methods Mentioned

BETA
transgenic
PCR
lavages
PMA
FACS
confocal microscopy
ELISA
flow cytometry
electrophoresis

Software Mentioned

FlowJo
Bioprofil
GraphPadPrism4
FlowJo Tree Star
FlowJo Star
Bio
Rad CFX Manager
GraphPad

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