{"id":31750,"date":"2025-05-10T10:52:19","date_gmt":"2025-05-10T08:52:19","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/05\/10\/itaconate-has-limited-protective-effects-in-experimental-malaria-models-valuefran-prenen-emilie-pollenus-hanne-meers-sofie-knoops-rebecca-sadler-margot-deckers-evanna-l-mills\/"},"modified":"2025-05-10T10:52:19","modified_gmt":"2025-05-10T08:52:19","slug":"itaconate-has-limited-protective-effects-in-experimental-malaria-models-valuefran-prenen-emilie-pollenus-hanne-meers-sofie-knoops-rebecca-sadler-margot-deckers-evanna-l-mills","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/05\/10\/itaconate-has-limited-protective-effects-in-experimental-malaria-models-valuefran-prenen-emilie-pollenus-hanne-meers-sofie-knoops-rebecca-sadler-margot-deckers-evanna-l-mills\/","title":{"rendered":"Itaconate Has Limited Protective Effects in Experimental Malaria Models. [[{&#8220;value&#8221;:&#8221;Fran Prenen, \nEmilie Pollenus, \nHanne Meers, \nSofie Knoops, \nRebecca Sadler, \nMargot Deckers, \nEvanna L. Mills, \nPhilippe E. Van den Steen&#8221;}]]"},"content":{"rendered":"<p><img decoding=\"async\" src=\"https:\/\/onlinelibrary.wiley.com\/cms\/asset\/75dcc2dd-c54e-4a64-9753-f6d9953367a5\/eji5981-gra-0001-m.png\" alt=\"Itaconate Has Limited Protective Effects in Experimental Malaria Models\" \/><\/p>\n<p>During <i>Plasmodium<\/i> infection, inflammatory monocytes upregulate ACOD1, leading to increased production of the anti-inflammatory metabolite itaconate. While ACOD1 deletion has no effect in the lethal <i>Pb<\/i>NK65-E model, it exacerbates disease in the milder <i>Pc<\/i>AS model. These findings highlight a modest but context-dependent protective role for itaconate in malaria. <\/p>\n<p><\/p>\n<h2>ABSTRACT<\/h2>\n<p>In severe malaria, dysregulated metabolism and excessive inflammatory responses contribute to fatal outcomes. Therapeutic strategies that address both metabolic and inflammatory balances are thus required. Itaconate, a metabolite produced by aconitate decarboxylase 1 (ACOD1), is a potent inhibitor of both inflammation and glycolysis with protective effects in various inflammatory diseases. Although elevated itaconate levels have been observed in <i>Plasmodium<\/i>-infected individuals, its role in malaria is still poorly understood, making further investigation essential for assessing its therapeutic potential. We investigated the role of itaconate in both severe and mild malaria using <i>Plasmodium berghei<\/i> NK65 (<i>Pb<\/i>NK65) and <i>Plasmodium chabaudi<\/i> AS (<i>Pc<\/i>AS) models, respectively. Using <sup>13<\/sup>C-tracer metabolomics, we detected increased itaconate levels in various organs during infection and identified inflammatory monocytes as the source of this production. Nevertheless, ACOD1 knockout mice displayed no significant changes in phenotype after <i>Pb<\/i>NK65 infection, and treatment of <i>Pb<\/i>NK65-infected mice with 4-octyl itaconate did not affect disease severity either. However, in the <i>Pc<\/i>AS model, ACOD1 deficiency worsened the disease, as indicated by increased weight loss, higher clinical scores, and elevated parasitemia. Therefore, in contrast to the findings in recent literature, our study shows that itaconate does not contribute to susceptibility, but rather provides limited protection to malaria.<\/p>","protected":false},"excerpt":{"rendered":"<p>During Plasmodium infection, inflammatory monocytes upregulate ACOD1, leading to increased production of the anti-inflammatory metabolite itaconate. While ACOD1 deletion has no effect in the lethal PbNK65-E model, it exacerbates disease in the milder PcAS model. These findings highlight a modest but context-dependent protective role for itaconate in malaria. ABSTRACT In severe malaria, dysregulated metabolism and &#8230; <a title=\"Itaconate Has Limited Protective Effects in Experimental Malaria Models. [[{&#8220;value&#8221;:&#8221;Fran Prenen, \nEmilie Pollenus, \nHanne Meers, \nSofie Knoops, \nRebecca Sadler, \nMargot Deckers, \nEvanna L. Mills, \nPhilippe E. Van den Steen&#8221;}]]\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/05\/10\/itaconate-has-limited-protective-effects-in-experimental-malaria-models-valuefran-prenen-emilie-pollenus-hanne-meers-sofie-knoops-rebecca-sadler-margot-deckers-evanna-l-mills\/\" aria-label=\"Read more about Itaconate Has Limited Protective Effects in Experimental Malaria Models. [[{&#8220;value&#8221;:&#8221;Fran Prenen, \nEmilie Pollenus, \nHanne Meers, \nSofie Knoops, \nRebecca Sadler, \nMargot Deckers, \nEvanna L. Mills, \nPhilippe E. Van den Steen&#8221;}]]\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[112,42],"tags":[],"class_list":["post-31750","post","type-post","status-publish","format-standard","hentry","category-european-journal-of-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/31750","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=31750"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/31750\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=31750"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=31750"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=31750"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}