Systemic lupus erythematosus-associated defects in the inhibitory receptor FcγRIIb reduce susceptibility to malaria

被引:136
作者
Clatworthy, Menna R.
Willcocks, Lisa
Urban, Britta
Langhorne, Jean
Williams, Tom N.
Peshu, Norbert
Watkins, Nicholas A.
Floto, R. Andres
Smith, Kenneth G. C. [1 ]
机构
[1] Cambridge Inst Med Res, Cambridge CB2 1TN, England
[2] Univ Cambridge, Dept Med, Cambridge CB2 1TN, England
[3] Univ Cambridge, Dept Haematol, Cambridge CB2 1TN, England
[4] Univ Oxford, Nuffield Dept Clin Med, Ctr Clin Vaccinol & Trop Med, Oxford OX1 2JD, England
[5] Natl Inst Med Res, Div Parasitol, London NW7 1AA, England
[6] Ctr Geog Med Res, Coast, Kenya
基金
英国惠康基金; 英国医学研究理事会;
关键词
autoimmunity; evolution; Fc gamma receptors;
D O I
10.1073/pnas.0608889104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Polygenic autoimmune diseases, such as systemic lupus erythematosus (SLE), are a significant cause of morbidity and mortality worldwide. In recent years, functionally important genetic polymorphisms conferring susceptibility to SLE have been identified, but the evolutionary pressures driving their retention in the gene pool remain elusive. A defunctioning, SLE-associated polymorphism of the inhibitory receptor Fc gamma RIIb is found at an increased frequency in African and Asian populations, broadly corresponding to areas where malaria is endemic. Here, we show that Fc gamma RIIb-deficient mice have increased clearance of malarial parasites (Plasmodium chabaudi chabaudi) and develop less severe disease. In vitro, the human lupus associated Fc gamma RIIb polymorphism enhances phagocytosis of Plasmodium falciparum-infected erythrocytes. These results demonstrate that Fc gamma RIIb is important in controlling the immune response to malarial parasites and suggests that the higher frequency of human Fc gamma RIIb polymorphisms predisposing to SLE in Asians and Africans may be maintained because these variants reduce susceptibility to malaria.
引用
收藏
页码:7169 / 7174
页数:6
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