Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Infect Dis. 2010 Jan 1;201(1):142-52. doi: 10.1086/648596.
Interethnic differences in susceptibility to malaria provide a unique opportunity to explore immunological correlates of protection. The Fulani of Sahelian Africa are known for their reduced susceptibility to Plasmodium falciparum, compared with surrounding tribes, yet the immunology underlying this is still poorly understood.
Here, we show that mononuclear cells from Fulani elicit >10-fold stronger interferon (IFN)-gamma production following a 24-h in vitro coincubation with asexual parasites than cells from sympatric Dogon. This response appears to be specific for P. falciparum among a panel of other human pathogens and is independent of the lower number of regulatory T cell counts present in Fulani. IFN-gamma responses in both tribes were inversely correlated with peripheral parasite density as quantified by nucleic acid sequenced-based amplification, but responses of Fulani remained significantly stronger than those of Dogon after adjustment for concurrent parasitemia, suggesting that hard-wired immunological differences underlie the observed protection.
These results underscore the value of early IFN-gamma responses to P. falciparum as a correlate of anti-parasite immunity, not only in this setting but also in the wider context of malaria, and support the development of malaria vaccines aimed at inducing such responses.
不同种族对疟疾的易感性差异为探索保护的免疫相关性提供了独特的机会。与周围部落相比，萨赫勒非洲的富拉尼人已知对疟原虫的易感性降低，但这背后的免疫学机制仍知之甚少。
在这里，我们表明，与来自同域的多贡人相比，富拉尼人的单核细胞在与无性体寄生虫共孵育 24 小时后，会产生超过 10 倍的干扰素（IFN）-γ。这种反应似乎是针对疟原虫的，而不是针对其他人类病原体的，并且与富拉尼人中存在的调节性 T 细胞计数较少无关。在两个部落中，IFN-γ反应与通过核酸序列扩增定量的外周寄生虫密度呈负相关，但在调整同期寄生虫血症后，富拉尼人的反应仍然明显强于多贡人的反应，这表明观察到的保护是由固有的免疫差异引起的。
这些结果强调了早期 IFN-γ 对疟原虫的反应作为抗寄生虫免疫的相关性，不仅在这种情况下，而且在更广泛的疟疾背景下，也支持开发旨在诱导这种反应的疟疾疫苗。
