A central role for free heme in the pathogenesis of severe malaria: the missing link?

摘要: Malaria, the disease caused by Plasmodium infection, is endemic to poverty in so-called underdeveloped countries. falciparum, main infectious species sub-Saharan countries, can trigger development of severe malaria, including cerebral a neurological syndrome that claims lives more than one million children (<5 years old) per year. Attempts eradicate and particular its lethal outcomes, have so far been unsuccessful. Using well-established rodent models malaria we found survival Plasmodium-infected host strictly dependent on host’s ability up-regulate expression heme oxygenase-1 (HO-1 encoded gene Hmox1). HO-1 stress-responsive enzyme catabolizes free into biliverdin, via reaction releases Fe generates gas carbon monoxide (CO). Generation CO through catabolism prevents onset malaria. The protective effect mediated binding cell-free hemoglobin (Hb) released from infected red blood cells during stage infection. Binding Hb release thus generation heme, which play central role pathogenesis We will address hereby how defense mechanisms prevent deleterious effects HO-1, impact pathologic outcome infection these may be used therapeutically suppress outcomes.