Giardia duodenalis MIF induces host intestinal damage via CD74 receptor mediated NLRP3 inflammasome activation

Duodenum is an important zoonotic protozoan that primarily causes diarrhea and has a significant negative impact on global public health. There are very few Enterobacteria. Infiguration and adaptive immune response of macrophage migration inhibitory factor (MIF) as an inflammatory mediator, the role of duodenal macrophage migration inhibitory factor (GdMIF) in host injury is now studied to induce CD74-NF-κB-NLRP3 inflammasome activation of GdMIF in vitro and in vivo and its effect on intestinal injury in the duodenum in study. We found that GdMIF is an exocrine protein with dopamine tautomerase activity. GdMIF activates eNF-κB and NLRP3 inflammasomes, increases the release of eGSDMD-NT fragments and lactate dehydrogenase (LDH), and promotes the production of e-pro-inflammatory cytokines. Interaction CD74 molecule Co-IP and BiFC validation. In addition, low CD74 and NF-κB significantly inhibit the production of pro-inflammatory cytokines in macrophages. Gerbils infected with duodenum blocked by GdMIF had lower NLRP3 expression and milder intestinal damage than Denal birch. Inhibition of NLRP3 may reduce Enterobacter denites infection In summary, GdMIF induces NLRP3 inflammasome activation and pyroptosis by interacting with CD74 receptors, which in turn triggers a pro-inflammatory response and leads to intestinal damage.