OBJECTIVE To investigate the role and mechanism of CD47-signal regulatory protein α （SIRPα） axis-mediated macrophage dysfunction in the immune tolerance of alveolar echinococcosis （AE）.

METHODS Immunohistochemistry was conducted to detect the expression of CD47 and SIRPα in the close liver tissues （CLT） and distal liver tissues （DLT） of 48 AE patients. RAW264.7 cells were co-cultured with protoscoleces in a control group, a co-culture group and an inhibitor group. Flow cytometry was performed to evaluate the phagocytic ability and polarization of the cells. Sixty mice were randomly divided into a control group, an AE group and an anti-CD47 group （each n=20）. The AE model was developed by injecting protoscoleces into the hepatic portal vein. Ten mice were randomly selected from each group to detect the liver-to-weight ratio and the surface area of parasitic cysts. Flow cytometry was performed to detect the polarization of hepatic macrophages and the proportions of splenic Th1 and Treg cells in the remaining mice of each group. The effect of hepatic macrophages on CD4⁺ T cell proliferation was assessed by mixed lymphocyte reaction.

RESULTS In AE patients, the expression levels of CD47 and SIRPα in the CLT were significantly higher than those in the DLT （P＜0.05）. In vitro examination revealed that, compared with the control group, both the co-culture group and the inhibitor group exhibited decreased positive rates of enhanced green fluorescent protein （EGFP）, along with increased proportions of M1 and M2 macrophages （P＜0.05）. Furthermore, relative to the co-culture group, the inhibitor group showed increased EGFP-positive rate and M1 proportion, but a decreased M2 proportion （P＜0.05）. In vivo examination showed that, compared with the control group, both the AE group and the anti-CD47 group had elevated liver-to-body weight ratio, proportions of M1, M2, Th1 and Treg cells, as well as increased positive rates of carboxyfluorescein diacetate succinimidyl ester （CFSE） （P＜ 0.05）. Moreover, relative to the AE group, the anti-CD47 group demonstrated reductions in liver-to-body weight ratio, parasitic cyst surface area and proportions of M2 and Treg cells, while the M1 and Th1 cell proportions and CFSE-positive rates were increased （P＜ 0.05）.

CONCLUSION Alveolar echinococcus may drive M2 polarization of macrophages through the CD47-SIRPα axis, thereby promoting immune tolerance in AE.