Open AccessMalaria inflammation by xanthine oxidase‐produced reactive oxygen species
Author(s) -
Ty Maureen C,
Zuniga Marisol,
Götz Anton,
Kayal Sriti,
Sahu Praveen K,
Mohanty Akshaya,
Mohanty Sanjib,
Wassmer Samuel C,
Rodriguez Ana
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809903
Subject(s) - inflammation , inflammasome , reactive oxygen species , xanthine oxidase , immunology , cerebral malaria , cytokine , macrophage , plasmodium falciparum , biology , malaria , nadph oxidase , proinflammatory cytokine , microbiology and biotechnology , in vitro , biochemistry , enzyme
Malaria is a highly inflammatory disease caused by Plasmodium infection of host erythrocytes. However, the parasite does not induce inflammatory cytokine responses in macrophages in vitro and the source of inflammation in patients remains unclear. Here, we identify oxidative stress, which is common in malaria, as an effective trigger of the inflammatory activation of macrophages. We observed that extracellular reactive oxygen species ( ROS ) produced by xanthine oxidase ( XO ), an enzyme upregulated during malaria, induce a strong inflammatory cytokine response in primary human monocyte‐derived macrophages. In malaria patients, elevated plasma XO activity correlates with high levels of inflammatory cytokines and with the development of cerebral malaria. We found that incubation of macrophages with plasma from these patients can induce a XO ‐dependent inflammatory cytokine response , identifying a host factor as a trigger for inflammation in malaria. XO ‐produced ROS also increase the synthesis of pro‐ IL ‐1β, while the parasite activates caspase‐1, providing the two necessary signals for the activation of the NLRP 3 inflammasome. We propose that XO ‐produced ROS are a key factor for the trigger of inflammation during malaria.