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Updated: Aug 14, 2026

Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases
Published on: November 22, 2024
Metabolite-effector immunity against malaria
Miguel P Soares1, Miguel Mesquita2, Ana Figueiredo2
1Gulbenkian Institute for Molecular Medicine (GIMM), Avenida Professor Egas Moniz, 1649-035 Lisboa, Portugal; Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-035 Lisboa, Portugal.
Abstract:
Jaundice, caused by the accumulation of bilirubin in plasma, is clinically interpreted as a maladaptive consequence of hemolysis or as indicative of hepatic failure. Drawing on genetic, biochemical, and clinical evidence, we propose to reframe jaundice as an adaptive response to malaria, a hemolytic disease caused by Plasmodium spp. infection. Bilirubin, the molecular basis of jaundice, represents an effector arm of metabolic immunity, distinct from nutritional immunity, which restricts pathogen access to essential nutrients, and from immunometabolism, which shapes immune cell function. In this opinion article, we outline bilirubin's multitarget antiplasmodial mechanisms, define its protective threshold, and discuss its evolutionary implications. We propose metabolite-effector immunity as a broadly applicable framework for host-pathogen biology.
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