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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 3; pp. 1122 - 1127
• Main Authors: Waisberg, Michael, Tarasenko, Tatyana, Vickers, Brandi K., Scott, Bethany L., Willcocks, Lisa C., Molina-Cruz, Alvaro, Pierce, Matthew A., Huang, Chiung-yu, Torres-Velez, Fernando J., Smith, Kenneth G. C., Barillas-Mury, Carolina, Miller, Louis H., Pierce, Susan K., Bolland, Silvia
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18-01-2011; National Acad Sciences
• Subjects: African Americans; African Continental Ancestry Group - genetics; Animals; Autoimmune diseases; Biological Sciences; Brain - immunology; Brain - pathology; Cerebral malaria; Cytokines; Cytokines - blood; DNA Primers - genetics; Enzyme-Linked Immunosorbent Assay; Erythrocytes - parasitology; Female; Flow Cytometry; Gene expression; Genetic Predisposition to Disease - genetics; Genetics; Humans; Immunology; Infections; Lupus; Lupus Erythematosus, Systemic - ethnology; Lupus Erythematosus, Systemic - genetics; Malaria; Malaria, Cerebral - genetics; Malaria, Cerebral - immunology; Malaria, Cerebral - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Organ Size; Parasitemia; Parasitic protozoa; Plasmodium berghei - immunology; Plasmodium falciparum; Receptors, IgG - deficiency; Receptors, IgG - genetics; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Spleen; Spleen - physiology; Survival Analysis; Systemic lupus erythematosus; T lymphocytes; Toll-Like Receptor 7 - metabolism; Women
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1017996108

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.