Oncotarget

Research Papers:

TLR2/MyD88 pathway-dependent regulation of dendritic cells by dengue virus promotes antibody-dependent enhancement via Th2-biased immunity

Junu Aleyas George, Seong Bum Kim, Jin Young Choi, Ajit Mahadev Patil, Ferdaus Mohd Altaf Hossain, Erdenebelig Uyangaa, Jin Hur, Sang-Youel Park, John-Hwa Lee, Koanhoi Kim and Seong Kug Eo _

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Oncotarget. 2017; 8:106050-106070. https://doi.org/10.18632/oncotarget.22525

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Abstract

Junu Aleyas George1,*, Seong Bum Kim1,*, Jin Young Choi1,*, Ajit Mahadev Patil1, Ferdaus Mohd Altaf Hossain1, Erdenebelig Uyangaa1, Jin Hur1, Sang-Youel Park1, John-Hwa Lee1, Koanhoi Kim2 and Seong Kug Eo1

1College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea

2Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea

*These authors have contributed equally to this work.

Correspondence to:

Seong Kug Eo, email: vetvirus@chonbuk.ac.kr

Keywords: dengue virus; Th2-type immunity; antibody-dependent enhancement; toll-like receptor; dendritic cells

Received: July 11, 2017     Accepted: October 28, 2017     Published: November 20, 2017

ABSTRACT

Possible risk mediators in primary dengue virus (DenV) infection that favor secondary DenV infection to life-threatening dengue hemorrhagic fever (DHF) and shock syndrome (DSS) via antibody-dependent enhancement (ADE) have not yet been described. Here, DenV infection enhanced the expression of inflammatory mediators and activation molecules in dendritic cells (DCs) through TLR2/MyD88 pathway. TLR2 appeared to facilitate DenV infection in DCs that were less permissive than macrophages for viral replication. In experiments using separate evaluations of DenV-infected and uninfected bystander DCs, infected DCs showed impaired maturation accompanied with TLR2-dependent production of inflammatory cytokines, by which uninfected bystander DCs showed increased expression of co-stimulatory molecules. Differential phosphorylation of MAPK and STAT3 was also detected between DenV-infected and uninfected DCs. Furthermore, DenV infection stimulated Th2-polarized humoral and cellular immunity against foreign and DenV Ag via TLR2/MyD88 pathway, and DenV-infected DCs were revealed to facilitate Th2-biased immune responses in TLR2-dependent manner. TLR2/MyD88-mediated Th2-biased Ab responses to primary DenV infection increased the infectivity of secondary homotypic or heterotypic DenV via ADE. Collectively, these results indicate that TLR2/MyD88 pathway in DC-priming receptors can drive Th2-biased immune responses during primary DenV infection, which could favor secondary DenV infection to DHF/DSS via ADE.


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