Echinococcus multilocularis induces surface high expression of inhibitory killer immunoglobulin‐like receptor on natural killer cells

Abstract

Alveolar echinococcosis (AE) is a malignant and fatal parasitic disease caused by the larvae of Echinococcus multilocularis (E. multilocularis), which inhibits the activity and proliferation of natural killer (NK) cells. In this study, the functional alteration of hepatic NK cells and their related molecules were studied. The AE-infected patient’s tissue was fixed with formalin, embedded in paraffin, and stained with Masson’s trichrome or hematoxylin and eosin (H&E). Single cells from AE-infected patient or E. multilocularis-infected mice were blocked with Fc-receptor (FcR), and stained with monoclonal antibodies, including CD16, CD56, CD3, KIR2DL1, granzyme B, perforin, Interferon gamma (IFN-γ), and tumor necrosis factor-α (TNF- α) or isotype control, to measure molecules and cytokines of NK cells and analyzed by flow cytometry. The Sirius red staining was used to quantitate hepatic fibrosis by calculating quantitative collagen deposition. AE can adjust both the number of hepatic CD56+ NK cells andits KIR2DL1 expression processes. Moreover, the overexpression of KIR2DL1 in NK cells could downregulate the functioning of immune cells in the liver area close to parasitic lesions. The number and dysfunction of NK cells in E. multilocularis infection could be related to the molecule dynamics of cell surface inhibitory receptor Ly49A, leading to hepatic damage and progression of fibrosis. This study illustrated significant increase in hepatic fibrogenesisand apparent upregulation of hepatic CD56+ NK cell population and its KIR2DL1 expression in AE-infected patients. This opposite variation might be related to the impaired NK cells functioning, such as granzyme B, IFN-γ, and TNF-α secretion. In addition, the cell surface inhibitory receptor Ly49A was related to the intracellular cytokine secretion functions of NK cells.

The Impact of Processing and Extraction Methods on the Allergenicity of Targeted Protein Quantification as Well as Bioactive Peptides Derived from Egg

“…Epitopes on the protein sequence may be destroyed during processing to reduce IgE-binding capacity, and new epitopes can be created to improve IgE-binding capability. Consequently, it is essential to assess the impact of processing on the allergenicity of egg proteins [ 265 , 266 ].…”

The Important Roles of Natural Killer Cells in Liver Fibrosis

“…Factors such as pathogenic infection (e.g., infection of Echinococcus multilocularis), liver metabolic disorder (e.g., NAFLD), and tumor development can induce NK cell dysfunction, leading to liver fibrosis [11,84,85]. Some treatments have been shown to regulate NK cell function to inhibit liver fibrosis, such as alcohol dehydrogenase 3 (ADH3) inhibitors, mi-croRNAs, NKG2D activators, and natural products.…”

Phenotype and function of MAIT cells in patients with alveolar echinococcosis

“…The regulatory network of immune cells in the liver plays a vital role in maintaining tissue integrity and defending against infection. The E. multilocularis infection process stimulates both adaptive and innate immune responses in the host, where macrophages (7), NK cells (8), and T cells (9) regulate the immune response through different mechanisms for host defense (10). It has been shown that treatment based on immune checkpoints PD-1 (11), PD-L1 (12), and TIGIT (13,14) immunotherapy has potential for the treatment of AE disease but is still not practiced in the clinic.…”