title: Genetic susceptibility to systemic lupus erythematosus protects against cerebral malaria in mice.
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.
authors.affiliation: Laboratories of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Waisberg
authors.forename: Tatyana
authors.initials: T
authors.lastname: Tarasenko
authors.forename: Brandi K
authors.initials: BK
authors.lastname: Vickers
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Scott
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Willcocks
authors.forename: Alvaro
authors.initials: A
authors.lastname: Molina-Cruz
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Pierce
authors.forename: Chiung-yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Torres-Velez
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
authors.forename: Carolina
authors.initials: C
authors.lastname: Barillas-Mury
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Susan K
authors.initials: SK
authors.lastname: Pierce
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolland
mesh_terms: D000818:Animals; D044383:Black People / Q000235:genetics*; D001921:Brain / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D016779:Malaria, Cerebral / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D010962:Plasmodium berghei / Q000276:immunology*; D017452:Receptors, IgG / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000502:physiology; D016019:Survival Analysis; D051199:Toll-Like Receptor 7 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017931:DNA Primers; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG; D051199:Toll-Like Receptor 7