Cellular and molecular life sciences : CMLS · 2025
Blocking NKG2A in Echinococcus multilocularis infection partially relieves impairment of NK cell function of the host.
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Aierken Ayinuer, Aierken Aili, Aimulajiang Kalibixiati, Abulizi Abuduaini, Yuan Zhongdian, Liu Chang, Zhu Dalong, Zhao Hanyue, Aji Tuerganaili
Аннотация
BACKGROUND: Alveolar echinococcosis (AE) is a fatal zoonotic parasitic disease with biological characteristics similar to cancer. Although previous studies have reported immune dysfunction of Natural Killer (NK) cells due to other inhibitory receptors in AE, limited research has been conducted on the role of Natural Killer cell protein Group 2-A (NKG2A) in human NK cells.
METHODS AND RESULTS: Our study revealed upregulation of NKG2A expression in peripheral blood and liver tissue NK cells in patients with AE, which was accompanied by a decrease in the secretion of IFN-γ, TNF-α, and Granzyme B by these NK cells. When we blocked the NKG2A receptor during co-culture of NK cells with Echinococcus multilocularis (E. multilocularis) proteins in vitro, we observed increased secretion of IFN-γ, TNF-α, and Granzyme B by NK cells. This observation was further confirmed in an E. multilocularis-infected mice model, in which higher expression levels of NKG2A on NK cells were detected, accompanied by a reduction in IFN-γ, TNF-α and Granzyme B secretion from NK cells. Deletion of NK cells in an E. multilocularis-infected mice model clearly resulted in more aggressive disease progression. Conversely, blocking NKG2A on NK cells results in increased secretion of TNF-α, and Granzyme B by NK cells. Similar changes in NKG2A expression and NK cell quality were observed in a mice model of splenic NK cells, as well as the functional recovery of NK cells after blocking NKG2A.
CONCLUSION: Our results demonstrate the involvement of NKG2A in impaired NK cell function during E. multilocularis infection in both humans and mice, suggesting that targeting NKG2A through blockade has the potential to restore NK cell function against this infection.
METHODS AND RESULTS: Our study revealed upregulation of NKG2A expression in peripheral blood and liver tissue NK cells in patients with AE, which was accompanied by a decrease in the secretion of IFN-γ, TNF-α, and Granzyme B by these NK cells. When we blocked the NKG2A receptor during co-culture of NK cells with Echinococcus multilocularis (E. multilocularis) proteins in vitro, we observed increased secretion of IFN-γ, TNF-α, and Granzyme B by NK cells. This observation was further confirmed in an E. multilocularis-infected mice model, in which higher expression levels of NKG2A on NK cells were detected, accompanied by a reduction in IFN-γ, TNF-α and Granzyme B secretion from NK cells. Deletion of NK cells in an E. multilocularis-infected mice model clearly resulted in more aggressive disease progression. Conversely, blocking NKG2A on NK cells results in increased secretion of TNF-α, and Granzyme B by NK cells. Similar changes in NKG2A expression and NK cell quality were observed in a mice model of splenic NK cells, as well as the functional recovery of NK cells after blocking NKG2A.
CONCLUSION: Our results demonstrate the involvement of NKG2A in impaired NK cell function during E. multilocularis infection in both humans and mice, suggesting that targeting NKG2A through blockade has the potential to restore NK cell function against this infection.