Unknown

Dataset Information

0

Oxidative insult can induce malaria-protective trait of sickle and fetal erythrocytes.


ABSTRACT: Plasmodium falciparum infections can cause severe malaria, but not every infected person develops life-threatening complications. In particular, carriers of the structural haemoglobinopathies S and C and infants are protected from severe disease. Protection is associated with impaired parasite-induced host actin reorganization, required for vesicular trafficking of parasite-encoded adhesins, and reduced cytoadherence of parasitized erythrocytes in the microvasculature. Here we show that aberrant host actin remodelling and the ensuing reduced cytoadherence result from a redox imbalance inherent to haemoglobinopathic and fetal erythrocytes. We further show that a transient oxidative insult to wild-type erythrocytes before infection with P. falciparum induces the phenotypic features associated with the protective trait of haemoglobinopathic and fetal erythrocytes. Moreover, pretreatment of mice with the pro-oxidative nutritional supplement menadione mitigate the development of experimental cerebral malaria. Our results identify redox imbalance as a causative principle of protection from severe malaria, which might inspire host-directed intervention strategies.

SUBMITTER: Cyrklaff M 

PROVIDER: S-EPMC5105170 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications


Plasmodium falciparum infections can cause severe malaria, but not every infected person develops life-threatening complications. In particular, carriers of the structural haemoglobinopathies S and C and infants are protected from severe disease. Protection is associated with impaired parasite-induced host actin reorganization, required for vesicular trafficking of parasite-encoded adhesins, and reduced cytoadherence of parasitized erythrocytes in the microvasculature. Here we show that aberrant  ...[more]

Similar Datasets

| S-EPMC4397954 | biostudies-literature
| S-EPMC5558763 | biostudies-other
| S-EPMC8221791 | biostudies-literature
| S-EPMC8024585 | biostudies-literature
| S-EPMC4460506 | biostudies-literature
| S-EPMC3541015 | biostudies-literature
| S-EPMC3880739 | biostudies-literature
| S-EPMC8526756 | biostudies-literature
| S-EPMC6269544 | biostudies-literature
| S-EPMC6048551 | biostudies-literature