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- W2041995719 endingPage "e1003327" @default.
- W2041995719 startingPage "e1003327" @default.
- W2041995719 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." @default.
- W2041995719 created "2016-06-24" @default.
- W2041995719 creator A5012815299 @default.
- W2041995719 creator A5025863770 @default.
- W2041995719 creator A5077368366 @default.
- W2041995719 date "2013-05-16" @default.
- W2041995719 modified "2023-10-11" @default.
- W2041995719 title "Hemoglobinopathies: Slicing the Gordian Knot of Plasmodium falciparum Malaria Pathogenesis" @default.
- W2041995719 cites W1490906959 @default.
- W2041995719 cites W1550705420 @default.
- W2041995719 cites W1586942665 @default.
- W2041995719 cites W1603028832 @default.
- W2041995719 cites W1624420511 @default.
- W2041995719 cites W1805406405 @default.
- W2041995719 cites W1908913108 @default.
- W2041995719 cites W1964149115 @default.
- W2041995719 cites W1965094767 @default.
- W2041995719 cites W1969180772 @default.
- W2041995719 cites W1969503178 @default.
- W2041995719 cites W1971705093 @default.
- W2041995719 cites W1973200069 @default.
- W2041995719 cites W1974074965 @default.
- W2041995719 cites W1976804468 @default.
- W2041995719 cites W1984270295 @default.
- W2041995719 cites W1987002047 @default.
- W2041995719 cites W1992496526 @default.
- W2041995719 cites W2001075170 @default.
- W2041995719 cites W2002887973 @default.
- W2041995719 cites W2003271897 @default.
- W2041995719 cites W2003472864 @default.
- W2041995719 cites W2004551743 @default.
- W2041995719 cites W2004883880 @default.
- W2041995719 cites W2005234042 @default.
- W2041995719 cites W2005645711 @default.
- W2041995719 cites W2007745105 @default.
- W2041995719 cites W2009943836 @default.
- W2041995719 cites W2012758550 @default.
- W2041995719 cites W2014574212 @default.
- W2041995719 cites W2019712983 @default.
- W2041995719 cites W2021650047 @default.
- W2041995719 cites W2021874649 @default.
- W2041995719 cites W2022161207 @default.
- W2041995719 cites W2022307600 @default.
- W2041995719 cites W2023824803 @default.
- W2041995719 cites W2025928231 @default.
- W2041995719 cites W2029010155 @default.
- W2041995719 cites W2031139287 @default.
- W2041995719 cites W2032597915 @default.
- W2041995719 cites W2033414054 @default.
- W2041995719 cites W2037217034 @default.
- W2041995719 cites W2037299483 @default.
- W2041995719 cites W2039227742 @default.
- W2041995719 cites W2039274105 @default.
- W2041995719 cites W2041342898 @default.
- W2041995719 cites W2042433863 @default.
- W2041995719 cites W2043107447 @default.
- W2041995719 cites W2043490826 @default.
- W2041995719 cites W2048992607 @default.
- W2041995719 cites W2049700891 @default.
- W2041995719 cites W2051143777 @default.
- W2041995719 cites W2051664736 @default.
- W2041995719 cites W2052523483 @default.
- W2041995719 cites W2053733754 @default.
- W2041995719 cites W2054221800 @default.
- W2041995719 cites W2059682385 @default.
- W2041995719 cites W2062003599 @default.
- W2041995719 cites W2063485848 @default.
- W2041995719 cites W2076000327 @default.
- W2041995719 cites W2076139670 @default.
- W2041995719 cites W2076653515 @default.
- W2041995719 cites W2079348110 @default.
- W2041995719 cites W2085541452 @default.
- W2041995719 cites W2092422689 @default.
- W2041995719 cites W2093866426 @default.
- W2041995719 cites W2099934028 @default.
- W2041995719 cites W2102446851 @default.
- W2041995719 cites W2102457341 @default.
- W2041995719 cites W2102823978 @default.
- W2041995719 cites W2104900016 @default.
- W2041995719 cites W2105252791 @default.
- W2041995719 cites W2107646820 @default.
- W2041995719 cites W2108089603 @default.
- W2041995719 cites W2108476551 @default.
- W2041995719 cites W2108555819 @default.
- W2041995719 cites W2108834482 @default.
- W2041995719 cites W2111913495 @default.
- W2041995719 cites W2111973713 @default.
- W2041995719 cites W2114550569 @default.
- W2041995719 cites W2116984096 @default.
- W2041995719 cites W2121739093 @default.
- W2041995719 cites W2124892357 @default.
- W2041995719 cites W2127952767 @default.
- W2041995719 cites W2128312300 @default.
- W2041995719 cites W2131163323 @default.
- W2041995719 cites W2131407151 @default.
- W2041995719 cites W2131868847 @default.
- W2041995719 cites W2132140005 @default.
- W2041995719 cites W2135625883 @default.