Laboratories of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1122-7. doi: 10.1073/pnas.1017996108. Epub 2010 Dec 27.
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.
恶性疟原虫对能够提高严重疟疾感染存活率的基因施加了巨大的选择压力。系统性红斑狼疮（SLE）是一种自身免疫性疾病，非洲裔女性的发病率比欧洲裔女性高六到八倍。在这里，我们提供的证据表明，SLE 的遗传易感性可预防脑型疟疾。由于 FcγRIIB 缺乏或 Toll 样受体 7 过度表达而容易患 SLE 的小鼠，可免受脑型疟疾导致的死亡。这种保护似乎是通过免疫机制实现的，使易患 SLE 的小鼠能够更好地控制其对寄生虫感染的整体炎症反应。这些发现表明，生活在非洲以外的非洲裔女性中 SLE 高发可能是由于遗传了对脑型疟疾的免疫控制有益的基因，但在没有疟疾的情况下，这些基因会导致自身免疫性疾病。
