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Metabolite-effector immunity against malaria.

Created on 13 Aug 2026

Authors

Miguel P Soares, Miguel Mesquita, Ana Figueiredo

Published in

Trends in parasitology. Aug 12, 2026. Epub Aug 12, 2026.

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.

PMID:
42586856
Bibliographic data and abstract were imported from PubMed on 13 Aug 2026.

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