Malaria inflammation by xanthine oxidase‐produced reactive oxygen species

Autor: Maureen C. Ty, Marisol Zuniga, Sriti Kayal, Anton Götz, Samuel C. Wassmer, Sanjib Mohanty, Praveen K. Sahu, Akshaya K Mohanty, Ana Rodriguez
Rok vydání: 2019
Předmět:
0301 basic medicine
Medicine (General)
medicine.medical_treatment
QH426-470
medicine.disease_cause
chemistry.chemical_compound
0302 clinical medicine
oxidative stress
Malaria
Falciparum
Cells
Cultured
reactive oxygen species
Chemistry
Caspase 1
Inflammasome
Articles
Microbiology
Virology & Host Pathogen Interaction
3. Good health
Cytokine
Cerebral Malaria
Host-Pathogen Interactions
Cytokines
Molecular Medicine
Inflammation Mediators
medicine.symptom
Signal Transduction
medicine.drug
Xanthine Oxidase
Immunology
Plasmodium falciparum
malaria
Malaria
Cerebral
Inflammation
Article
Proinflammatory cytokine
03 medical and health sciences
R5-920
NLRP3
NLR Family
Pyrin Domain-Containing 3 Protein
parasitic diseases
Genetics
medicine
Humans
Xanthine oxidase
Macrophages
Macrophage Activation
medicine.disease
030104 developmental biology
030217 neurology & neurosurgery
Malaria
Oxidative stress
Zdroj: EMBO Molecular Medicine
EMBO Molecular Medicine, Vol 11, Iss 8, Pp n/a-n/a (2019)
ISSN: 1757-4684
1757-4676
DOI: 10.15252/emmm.201809903
Popis: 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 NLRP3 inflammasome. We propose that XO‐produced ROS are a key factor for the trigger of inflammation during malaria.
Databáze: OpenAIRE
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