当前位置： SCI文献检索 > PLoS Pathogens期刊下所有文献 > Hemoglobinopathies: slicing the Gordian knot of Plasmodium falciparum malaria pathogenesis.

Hemoglobinopathies: slicing the Gordian knot of Plasmodium falciparum malaria pathogenesis.

Abstract：

:Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits--including hemoglobin S (HbS), hemoglobin C (HbC), and α-thalassemia--are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70% by homozygous HbC and 90% by heterozygous HbS (sickle-cell trait). Importantly, this protection is principally present for severe disease and largely absent for P. falciparum infection, suggesting that these hemoglobinopathies specifically neutralize the parasite's in vivo mechanisms of pathogenesis. These hemoglobin variants thus represent a "natural experiment" to identify the cellular and molecular mechanisms by which P. falciparum produces clinical morbidity, which remain partially obscured due to the complexity of interactions between this parasite and its human host. Multiple lines of evidence support a restriction of parasite growth by various hemoglobinopathies, and recent data suggest this phenomenon may result from host microRNA interference with parasite metabolism. Multiple hemoglobinopathies mitigate the pathogenic potential of parasites by interfering with the export of P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of the host red blood cell. Few studies have investigated their effects upon the activation of the innate and adaptive immune systems, although recent murine studies suggest a role for heme oxygenase-1 in protection. Ultimately, the identification of mechanisms of protection and pathogenesis can inform future therapeutics and preventive measures. Hemoglobinopathies slice the "Gordian knot" of host and parasite interactions to confer malaria protection, and offer a translational model to identify the most critical mechanisms of P. falciparum pathogenesis.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Taylor SM,Cerami C,Fairhurst RM

doi

10.1371/journal.ppat.1003327

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

e1003327

issue

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-12-03054

journal_volume

pub_type

杂志文章,评审

在线工具

Hemoglobinopathies: slicing the Gordian knot of Plasmodium falciparum malaria pathogenesis.