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

BACKGROUND: Alveolar 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 importan...

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Autores principales: Abulizi, Abuduaini, Shao, Yingmei, Aji, Tuerganaili, Li, Zhide, Zhang, Chuanshan, Aini, Abudusalamu, Wang, Hui, Tuxun, Tuerhongjiang, Li, Liang, Zhang, Ning, Lin, Renyong, Wen, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734356/
https://www.ncbi.nlm.nih.gov/pubmed/31500589
http://dx.doi.org/10.1186/s12879-019-4417-1
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author Abulizi, Abuduaini
Shao, Yingmei
Aji, Tuerganaili
Li, Zhide
Zhang, Chuanshan
Aini, Abudusalamu
Wang, Hui
Tuxun, Tuerhongjiang
Li, Liang
Zhang, Ning
Lin, Renyong
Wen, Hao
author_facet Abulizi, Abuduaini
Shao, Yingmei
Aji, Tuerganaili
Li, Zhide
Zhang, Chuanshan
Aini, Abudusalamu
Wang, Hui
Tuxun, Tuerhongjiang
Li, Liang
Zhang, Ning
Lin, Renyong
Wen, Hao
author_sort Abulizi, Abuduaini
collection PubMed
description BACKGROUND: Alveolar 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. METHODS: 2000 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. RESULTS: The 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. CONCLUSIONS: Our 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4417-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-67343562019-09-12 Echinococcus multilocularis inoculation induces NK cell functional decrease through high expression of NKG2A in C57BL/6 mice Abulizi, Abuduaini Shao, Yingmei Aji, Tuerganaili Li, Zhide Zhang, Chuanshan Aini, Abudusalamu Wang, Hui Tuxun, Tuerhongjiang Li, Liang Zhang, Ning Lin, Renyong Wen, Hao BMC Infect Dis Research Article BACKGROUND: Alveolar 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. METHODS: 2000 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. RESULTS: The 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. CONCLUSIONS: Our 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4417-1) contains supplementary material, which is available to authorized users. BioMed Central 2019-09-09 /pmc/articles/PMC6734356/ /pubmed/31500589 http://dx.doi.org/10.1186/s12879-019-4417-1 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Abulizi, Abuduaini
Shao, Yingmei
Aji, Tuerganaili
Li, Zhide
Zhang, Chuanshan
Aini, Abudusalamu
Wang, Hui
Tuxun, Tuerhongjiang
Li, Liang
Zhang, Ning
Lin, Renyong
Wen, Hao
Echinococcus multilocularis inoculation induces NK cell functional decrease through high expression of NKG2A in C57BL/6 mice
title Echinococcus multilocularis inoculation induces NK cell functional decrease through high expression of NKG2A in C57BL/6 mice
title_full Echinococcus multilocularis inoculation induces NK cell functional decrease through high expression of NKG2A in C57BL/6 mice
title_fullStr Echinococcus multilocularis inoculation induces NK cell functional decrease through high expression of NKG2A in C57BL/6 mice
title_full_unstemmed Echinococcus multilocularis inoculation induces NK cell functional decrease through high expression of NKG2A in C57BL/6 mice
title_short Echinococcus multilocularis inoculation induces NK cell functional decrease through high expression of NKG2A in C57BL/6 mice
title_sort echinococcus multilocularis inoculation induces nk cell functional decrease through high expression of nkg2a in c57bl/6 mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734356/
https://www.ncbi.nlm.nih.gov/pubmed/31500589
http://dx.doi.org/10.1186/s12879-019-4417-1
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