{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:59:32Z","timestamp":1791331172933,"version":"4.3.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013968","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 32202834"],"award-info":[{"award-number":["No. 32202834"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013061","name":"Jilin Provincial Scientific and Technological Development Program","doi-asserted-by":"publisher","award":["20220202054NC"],"award-info":[{"award-number":["20220202054NC"]}],"id":[{"id":"10.13039\/501100013061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    <jats:italic>Giardia duodenalis<\/jats:italic>\n                    is an important zoonotic protozoan that mainly causes diarrhea, has a significant negative impact on public health worldwide. Macrophage migration inhibitory factor (MIF) as an inflammatory mediator in both innate and adaptive immune responses, and parasite-derived MIF is involved in inducing the host\u2019s immune response or causing disease. However, the role of\n                    <jats:italic>G. duodenalis<\/jats:italic>\n                    MIF (GdMIF) in giardiasis remains to be elucidated. In the present study, CD74-NF-\u03baB-NLRP3 inflammasome activation induced by rGdMIF was systematically investigated\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and its effect on intestinal damage was examined in\n                    <jats:italic>G. duodenalis-<\/jats:italic>\n                    infected gerbils. We found that GdMIF was an exocrine protein with dopamine tautomerase activity. GdMIF could activate NF-\u03baB and the NLRP3 inflammasome, increase GSDMD-processing and promote Lactate Dehydrogenase (LDH) and pro-inflammatory cytokine release. The interaction of CD74 molecule with rGdMIF was validated by Co-IP and BiFC. Furthermore, knockdown of CD74 and NF-\u03baB significantly inhibited NLRP3 inflammasome activation and pro-inflammatory cytokine production in macrophages stimulated by rGdMIF. Gerbils were infected with\n                    <jats:italic>G. duodenalis<\/jats:italic>\n                    in the presence of a GdMIF blocking antibody showed lower NLRP3 expression, and milder intestinal damage compared with that of the normal\n                    <jats:italic>G. duodenalis<\/jats:italic>\n                    infection group. Inhibition of NLRP3 alleviated intestinal damage caused by\n                    <jats:italic>G. duodenalis<\/jats:italic>\n                    infection. In summary, these findings suggest that GdMIF induces NLRP3 inflammasome activation and pyroptosis by interacting with CD74 receptor, subsequently eliciting a pro-inflammatory response which lead to intestinal damage.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0013968","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:55:56Z","timestamp":1770058556000},"page":"e0013968","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Giardia duodenalis MIF induces host intestinal damage via CD74 receptor mediated NLRP3 inflammasome 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