{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:27:57Z","timestamp":1791052077800,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,1,19]],"date-time":"2012-01-19T00:00:00Z","timestamp":1326931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In areas where polyparasitism is highly prevalent, the impact of multiple parasites on the host response is underestimated. In particular, the presence of helminth infection coincident with malaria profoundly alters the production of malaria\u2010specific IFN\u2010\u03b3, IL\u201012p70, CXCL9, CXCL10 and CXCL11, cytokines\/chemokines known to be critical in mediating malaria\u2010specific immunity. In order to elucidate the mechanisms underlying the suppression of malaria\u2010specific cytokines\/chemokines, we assessed the expression of malaria\u2010specific IL\u201012R\u03b21, IL\u201012R\u03b22 and interferon regulatory factor (IRF)\u20101 in blood obtained from 18 filaria\u2010infected (Fil<jats:sup>+<\/jats:sup>) and 17 filaria\u2010uninfected (Fil<jats:sup>\u2212<\/jats:sup>) individuals in a filaria\u2010malaria co\u2010endemic region of Mali. We found that Fil<jats:sup>+<\/jats:sup> individuals had significantly lower RNA expression of IRF\u20101 but not IL\u201012R\u03b21 or IL\u201012R\u03b22 in response to malaria antigen stimulation. We also measured the frequency of IL\u201012\u2010producing DCs from these subjects and found that Fil<jats:sup>+<\/jats:sup> subjects had lower frequencies of IL\u201012<jats:sup>+<\/jats:sup> mDCs after malaria antigen stimulation than did the Fil<jats:sup>\u2212<\/jats:sup> subjects. Modeling these data in vitro, we found that mDCs pre\u2010exposed to live microfilariae not only produced significantly lower levels of CXCL\u20109, CXCL\u201010, IL\u201012p35, IL\u201012p40, IL\u201012p19 and CXCL\u201011 following stimulation with malaria antigen but also markedly downregulated the expression of IRF\u20101, IRF\u20102 and IRF\u20103 compared with microfilaria\u2010unexposed mDCs. siRNA\u2010inhibition of <jats:italic>irf\u20101<\/jats:italic> in mDCs downregulated the production of IL\u201012p70 through repression of IL\u201012p35. Our data demonstrate that the modulation of IRFs seen in filarial (and presumably other tissue\u2010invasive helminths) infection underlies the suppression of malaria\u2010specific cytokines\/chemokines that play a crucial role in immunity to malaria.<\/jats:p>","DOI":"10.1002\/eji.201141991","type":"journal-article","created":{"date-parts":[[2011,12,24]],"date-time":"2011-12-24T23:45:02Z","timestamp":1324770302000},"page":"641-650","source":"Crossref","is-referenced-by-count":28,"title":["Interferon regulatory factor modulation underlies the bystander suppression of malaria antigen\u2010driven IL\u201012 and IFN\u2010\u03b3 in filaria\u2010malaria co\u2010infection"],"prefix":"10.1002","volume":"42","author":[{"given":"Simon","family":"Metenou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Dembele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaya I.","family":"Coulibaly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy D.","family":"Klion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Nutman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,19]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182008000346"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000412"},{"key":"e_1_2_1_4_2","unstructured":"WHO World Malaria Report2009. 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