Myeloperoxidase (MPO) exacerbates dengue-associated liver injury and contributes to disease pathogenesis in mouse models

Severe dengue can cause liver damage through unknown pathways. Researchers examined the involvement of myeloperoxidase (MPO), an enzyme produced by neutrophils, in dengue using patient data, fatal liver samples, and mouse models of infection. Two separate clinical studies found higher levels of MPO in the blood of dengue patients, and in one study, MPO was associated with liver injury markers during the disease's most critical stage.

Liver tissue from fatal dengue cases showed MPO accumulation near CD177+ activated neutrophils. In mice, dengue infection resulted in increased MPO expression, oxidative damage, and activation of inflammatory processes in the liver. Suppressing MPO activity lessened these effects and improved survival in one mouse model, while in another, it only delayed disease progression without preventing death.

These results demonstrate MPO as a functional contributor to severe dengue-associated liver injury and inflammation, suggesting it is a potential target for therapeutic intervention in further preclinical studies.