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Malaria parasites express a MIF homologue that might modulate host immune responses against blood-stage parasites, but the potential importance of MIF against other life cycle stages remains unstudied. In this study, we characterized the MIF homologue of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium yoelii<\/jats:named-content>throughout the life cycle, with emphasis on preerythrocytic stages.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. yoelii<\/jats:named-content>MIF (Py-MIF) was expressed in blood-stage parasites and detected at low levels in mosquito salivary gland sporozoites. MIF expression was strong throughout liver-stage development and localized to the cytoplasm of the parasite, with no evidence of release into the host hepatocyte. To examine the importance of Py-MIF for liver-stage development, we generated a Py<jats:italic>-mif<\/jats:italic>knockout parasite (<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. yoelii<\/jats:named-content>\u0394<jats:italic>mif<\/jats:italic>).<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. yoelii<\/jats:named-content>\u0394<jats:italic>mif<\/jats:italic>parasites grew normally as asexual erythrocytic-stage parasites and showed normal infection of mosquitoes. In contrast, the<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. yoelii<\/jats:named-content>\u0394<jats:italic>mif<\/jats:italic>strain was attenuated during the liver stage. Mice infected with<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. yoelii<\/jats:named-content>\u0394<jats:italic>mif<\/jats:italic>sporozoites either did not develop blood-stage parasitemia or exhibited a delay in the onset of blood-stage patency. Furthermore,<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. yoelii<\/jats:named-content>\u0394<jats:italic>mif<\/jats:italic>parasites exhibited growth retardation<jats:italic>in vivo<\/jats:italic>. Combined, the data indicate that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium<\/jats:named-content>MIF is important for liver-stage development of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. yoelii<\/jats:named-content>, during which it is likely to play an intrinsic role in parasite development rather than modulating host immune responses to infection.<\/jats:p>","DOI":"10.1128\/iai.05861-11","type":"journal-article","created":{"date-parts":[[2012,1,18]],"date-time":"2012-01-18T05:17:41Z","timestamp":1326863861000},"page":"1399-1407","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":54,"title":["Plasmodium yoelii Macrophage Migration Inhibitory Factor Is Necessary for Efficient Liver-Stage Development"],"prefix":"10.1128","volume":"80","author":[{"given":"Jessica L.","family":"Miller","sequence":"first","affiliation":[{"name":"Seattle Biomedical Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Harupa","sequence":"additional","affiliation":[{"name":"Seattle Biomedical Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H. 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