TLR3 Modulates the Response of NK Cells against Schistosoma japonicum.

Jiale Qu,Lu Li,Jun Huang,Huaina Qiu,Chenxi Jin,Hongyan Xie,Xiaona Zhang,Nuo Dong,Quan Yang,Yuanfa Feng

doi:10.1155/2018/7519856

Abstract

Natural killer (NK) cells are classic innate immune cells that play roles in many types of infectious diseases. NK cells possess many kinds of TLRs that allow them to sense and respond to invading pathogens. Our previous study found that NK cells could modulate the immune response induced by Schistosoma japonicum (S. japonicum) in C57BL/6 mice. In the present study, the role of TLRs in the progress of S. japonicum infection was investigated. Results showed that the expression of TLR3 on NK cells increased significantly after S. japonicum infection by using RT-PCR and FACS (P < 0.05). TLR3 agonist (Poly I:C) increased IFN-γ and IL-4 levels in the supernatant of cultured splenocytes and induced a higher percentage of IFN-γ- and IL-4-secreting NK cells from infected mouse splenocytes (P < 0.05). Not only the percentages of MHC II-, CD69-, and NKG2A/C/E-expressing cells but also the percentages of IL-4-, IL-5-, and IL-17-producing cells in TLR3+ NK cells increased significantly after infection (P < 0.05). Moreover, the expression of NKG2A/C/E, NKG2D, MHC II, and CD69 on the surface of splenic NK cells was changed in S. japonicum-infected TLR3−/− (TLR3 KO mice, P < 0.05); the abilities of NK cells in IL-4, IL-5, and IL-17 secretion were decreased too (P < 0.05). These results indicate that TLR3 is the primary molecule which modulates the activation and function of NK cells during the course of S. japonicum infection in C57BL/6 mice.

Highlights

Schistosomiasis japonica is a chronic helminth infection of humans caused by S. japonicum [1, 2]
The results demonstrated that the expressions of TLR2, TLR3, TLR4, and TLR7 mRNA in splenic natural killer (NK) cells significantly increased after S. japonicum infection (P < 0 05)
It was reported that NK cells could express many kinds of Toll-like receptors (TLRs), which could play an important role in the progress of NK cell activation in response to bacterial and viral infection [21] and tumors [24]

Summary

Introduction

Schistosomiasis japonica is a chronic helminth infection of humans caused by S. japonicum [1, 2]. The eggs of S. japonicum are deposited in the liver, lung, and intestinal wall and induce granulomatous inflammation and progressive fibrosis, which are the primary clinical pathological changes. NK cells are innate lymphocytes that respond rapidly to invading pathogens by exerting a direct cytotoxic effect or secreting various cytokines, interferon-gamma (IFN-γ) [7] Recent studies have reported that NK cells are able to survive long enough to take part in the adaptive immune response [9], and NK cells could play an important role in the immune response of host against pathogen and tumor [10] In parasite infection, both activated and inhibitory receptors such as CD16, CD69, NKG2D, and Ly49a on Journal of Immunology Research

Methods

Results

Conclusion