Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Macrophages induce natural killer cell dysfunction via KIR2DL1 during Echinococcus multilocularis infection

Bayindala ¹, Tuerganaili Aji¹, Bo Ran¹, Tieming Jiang¹, Wulan Tongbayier², Yingmei Shao¹

¹Department of Hepatic Hydatid and Hepatobiliary Surgery; ²Supply Room, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province 830011, China.

For correspondence:- Yingmei Shao Email: Shaoyinmei2019tt@163.com Tel:+869914362357

Accepted: 17 June 2019 Published: 29 July 2019

Citation: B, Aji T, Ran B, Jiang T, Tongbayier W, Shao Y. Macrophages induce natural killer cell dysfunction via KIR2DL1 during Echinococcus multilocularis infection. Trop J Pharm Res 2019; 18(7):1527-1532 doi: 10.4314/tjpr.v18i7.24

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the mechanism by which natural killer (NK) cells are compromised by infection with Echinococcus multilocularis in patients with alveolar echinococcosis (AE).

Methods: NK cells from AE patients and healthy individuals were measured by flow cytometry and quantitative real-time polymerase chain reaction (PCR) to identify the frequency of different types of NK cells and assess their function. E. multilocularis cyst fluid (EMF) was applied to human monocytic leukaemia cells (THP-1 cells) to assess its effect on their differentiation. In a co-culture system with NK and EMF-THP-1 cells, the function of NK cells were analyzed by enzyme-linked immunosorbent assay (ELISA) with or without antibody against KIR2DL1.

Results: Blood from AE patients had fewer CD56low NK cells (p < 0.01) with decreased production of IFN-γ and granzyme B due to the elevated expression of KIR2DL1 (p < 0.001). Treatment of THP-1 cells with EMF induced a tolerogenic phenotype upon activation. Incubation of these EMF-THP-1 cells with NK cells isolated from AE patients significantly impaired the cytotoxic function of NK cells, but this effect was largely blocked by an anti-KIR2DL1 antibody (p < 0.001).

Conclusion: E. multilocularis modulates infection macrophages to induce NK cell dysfunction via interaction with KIR2DL1. These results provide a new insight into the mechanisms of parasitic infection-induced dysfunction of NK cells, and may be helpful for the development of therapeutic strategies for the treatment of alveolar echinococcosis.

Keywords: Echinococcus multilocularis, Chronic helminthic diseases, Macrophages, NK cells, Killer-cell immunoglobulin-like receptors