Mitochondrial damage and IL-1β production in monocytes caused by

Introduction: The intracellular proliferation of Methods: In the infection of human monocytic cell line THP-1 cells with the Results: In the infection of THP-1 cells with the NcGRA7KO parasite, decreased IL-1β release was observed compared with Nc1 infection. Transfection with plasmids for reconstitution of the NLRP3 inflammasome enhanced IL-1b production via additional transfection with NcGRA7 cDNA. NLRP3 inhibitor, CASP1 inhibitor, and NF-κB inhibitor significantly suppressed IL-1β production induced by Nc-1 infection, whereas no inhibitory effect was observed in NcGRA7KO-infected cells. Furthermore, treatment with any of the inhibitors led to a reduction in TNF-α production in both Nc-1- and NcGRA7KO-infected cells. Western blot analysis of phosphorylated NF-κB p65 demonstrated that Discussion: These findings indicate that NcGRA7 does not directly modulate NF-κB activation but likely enhances the production of IL-1β and TNF-α through post-transcriptional mechanisms, thereby contributing to the upregulation of NLRP3 expression. Moreover, our results suggest that NcGRA7 influences both the NF-κB and inflammasome pathways through its interaction with host cell prohibitins. Elucidating the roles of PHB1 and NcGRA7 will provide new insights into the host-parasite interactions underlying