Echinococcus multilocularis inoculation induces NK cell functional decrease through high expression of NKG2A in C57BL/6 mice

Abuduaini Abulizi,Liang Li,Yingmei Shao,Chuanshan Zhang,Renyong Lin,Hui Wang,Ning Zhang,Tuerhongjiang Tuxun,Hao Wen,Abudusalamu Aini,Zhide Li,Tuerganaili Aji

doi:10.1186/s12879-019-4417-1

Abuduaini Abulizi, Liang Li + Show 10 more

Open Access

https://doi.org/10.1186/s12879-019-4417-1

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Abstract

BackgroundAlveolar echinococcosis (AE) is caused by the larval stage of Echinococcus multilocularis (E. multilocularis), and considered as public health issue. Parasite-host immune interaction is pivotal during infection. As a subset of innate lymphoid cells, NK cells are known to play an important role during virus, bacteria, intra/extracellular parasitic infections and tumor progression. However, the possible role of NK cells in E. multilocularis infection in both human and murine is little known. Herein, the functional alteration of hepatic NK cells and their related molecules in E. multilocularis infected mice were studied.Methods2000 protoscoleces (PSCs) were injected to C57BL/6 mice via the portal vein to establish secondary E. multilocularis infection. NK cells population and their related molecules (CD69, Ly49D, Ly49G2, Ly49H, Ly49I, NKG2A, NKG2D, granzyme B, IFN-γ, TNF-α) were assessed by using fluorescence-activated cell sorter (FACS) techniques and qRT-PCR. NK cell depletion was performed for further understanding the possible function of NK cells during infection.ResultsThe total frequencies of NK cells and NK-derived IFN-γ production were significantly reduced at designated time points (2, 4, 12 weeks). The liver resident (CD49a+DX5−) NK cells are decreased at 4 weeks after inoculation and which is significantly lower than in control mice. Moreover, in vivo antibody-mediated NK cell depletion increased parasitic load and decreased peri-parasitic fibrosis. Expression of the inhibitory receptor NKG2A was negatively related to NK- derived IFN-γ secretion.ConclusionsOur study showed down regulates of NK cells and upper regulates of NKG2A expression on NK cells during E. multilocularis infection. Reduction of NK cell frequencies and increased NKG2A might result in low cytotoxic activity through decreased IFN-γ secretion in E. multilocularis infection. This result might be helpful to restore NK cell related immunity against E. multilocularis infection to treat alveolar echinococcosis.

Highlights

Alveolar echinococcosis (AE) is caused by the larval stage of Echinococcus multilocularis (E. multilocularis), and considered as public health issue
NK cells population is markedly decreased in infected mice The hepatic NK cells population and IFN-γproduction were decreased respectively at 2, 4, 12 weeks post E. multilocularis inoculation, but at 24th week after infection no change was observed (Fig. 1a, b, c, d), while Tumor necrosis factor—α (TNF-α) and granzyme B levels had no significance in designated time points (Additional file 2: Figure S1)
We NK cells after infection. b Percentage of liver NK cells during the different time-points after infection. c Representative fluorescence-activated cell sorter (FACS) plots gated on percentages of liver NK cells secretion of IFN-γafter infection. d The percentages of liver NK cells secretion of IFN-γ during different time points after infection. e Representative FACS plots gated on percentage of CD49a+DX5− NK cells in liver NK cells after infection. f The percentage of CD49a+DX5− liver resident NK cells during the different time points after infection

Summary

Introduction

Alveolar echinococcosis (AE) is caused by the larval stage of Echinococcus multilocularis (E. multilocularis), and considered as public health issue. As a subset of innate lymphoid cells, NK cells are known to play an important role during virus, bacteria, intra/ extracellular parasitic infections and tumor progression. The possible role of NK cells in E. multilocularis infection in both human and murine is little known. The functional alteration of hepatic NK cells and their related molecules in E. multilocularis infected mice were studied. Alveolar echinococcosis, caused by the larval stage of E. multilocularis, continues to be a real world-wide public health issue. It is prevalent mainly in Western China, Middle East and as well as Central Europe [1]. The attempt to unveil the underlined mechanism of such an infiltrative disease, regarded as “parasitic cancer”, is vital important

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