Genetic susceptibility to systemic lupus erythematosus protects against cerebral malaria in mice

Michael Waisberg, Tatyana Tarasenko, Brandi K. Vickers, Bethany L. Scott, Lisa C. Willcocks, Alvaro Molina-Cruz, Matthew A. Pierce, Chiung Yu Huang, Fernando J. Torres-Velez, Kenneth G.C. Smith, Carolina Barillas-Mury, Louis H. Miller, Susan K. Pierce, Silvia Bolland

Research output: Contribution to journalArticlepeer-review

Abstract

Plasmodium falciparum has exerted tremendous selective pressure on genes that improve survival in severe malarial infections. Systemic lupus erythematosus (SLE) is an autoimmune disease that is six to eight times more prevalent in women of African descent than in women of European descent. Here we provide evidence that a genetic susceptibility to SLE protects against cerebral malaria. Mice that are prone to SLE because of a deficiency in FcγRIIB or overexpression of Toll-like receptor 7 are protected from death caused by cerebral malaria. Protection appears to be by immune mechanisms that allow SLE-prone mice better to control their overall inflammatory responses to parasite infections. These findings suggest that the high prevalence of SLE in women of African descent living outside of Africa may result from the inheritance of genes that are beneficial in the immune control of cerebral malaria but that, in the absence of malaria, contribute to autoimmune disease.

Original languageEnglish (US)
Pages (from-to)1122-1127
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number3
DOIs
StatePublished - Jan 18 2011

ASJC Scopus subject areas

  • General

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