Abstract：
:Hereditary xerocytosis is thought to be a rare genetic condition characterized by red blood cell (RBC) dehydration with mild hemolysis. RBC dehydration is linked to reduced Plasmodium infection in vitro; however, the role of RBC dehydration in protection against malaria in vivo is unknown. Most cases of hereditary xerocytosis are associated with gain-of-function mutations in PIEZO1, a mechanically activated ion channel. We engineered a mouse model of hereditary xerocytosis and show that Plasmodium infection fails to cause experimental cerebral malaria in these mice due to the action of Piezo1 in RBCs and in T cells. Remarkably, we identified a novel human gain-of-function PIEZO1 allele, E756del, present in a third of the African population. RBCs from individuals carrying this allele are dehydrated and display reduced Plasmodium infection in vitro. The existence of a gain-of-function PIEZO1 at such high frequencies is surprising and suggests an association with malaria resistance.
journal_name
Celljournal_title
Cellauthors
Ma S,Cahalan S,LaMonte G,Grubaugh ND,Zeng W,Murthy SE,Paytas E,Gamini R,Lukacs V,Whitwam T,Loud M,Lohia R,Berry L,Khan SM,Janse CJ,Bandell M,Schmedt C,Wengelnik K,Su AI,Honore E,Winzeler EA,Andersen KG,Patapoudoi
10.1016/j.cell.2018.02.047subject
Has Abstractpub_date
2018-04-05 00:00:00pages
443-455.e12issue
2eissn
0092-8674issn
1097-4172pii
S0092-8674(18)30224-1journal_volume
173pub_type
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