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

Autor: Liang Li, Abudusalamu Aini, Chuanshan Zhang, Ning Zhang, Yingmei Shao, Hui Wang, Zhide Li, Renyong Lin, Tuerhongjiang Tuxun, Hao Wen, Tuerganaili Aji, Abuduaini Abulizi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: BMC Infectious Diseases
BMC Infectious Diseases, Vol 19, Iss 1, Pp 1-12 (2019)
ISSN: 1471-2334
Popis: BackgroundAlveolar echinococcosis (AE) is caused by the larval stage ofEchinococcus 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 inE. multilocularisinfection in both human and murine is little known. Herein, the functional alteration of hepatic NK cells and their related molecules inE. multilocularisinfected mice were studied.Methods2000 protoscoleces (PSCs) were injected to C57BL/6 mice via the portal vein to establish secondaryE. multilocularisinfection.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 duringE. multilocularisinfection. Reduction of NK cell frequencies and increased NKG2A might result in low cytotoxic activity through decreased IFN-γ secretion inE. multilocularisinfection. This result might be helpful to restore NK cell related immunity againstE. multilocularisinfection to treat alveolar echinococcosis.
Databáze: OpenAIRE