McNitt Sarah A, Dick Jenna K, Hernandez-Castaneda Maria Andrea, Sangala Jules, Pierson Mark, Macchietto Marissa, Burrack Kristina S, Crompton Peter D, Seydel Karl, Hamilton Sara E, Hart Geoffrey T
Department of Osteopathic Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, USA.
Division of Infectious Disease and Internal Medicine, Department of Medicine.
JCI Insight. 2025 May 8;10(9). doi: 10.1172/jci.insight.183076.
P.falciparum infection can trigger high levels of inflammation that lead to fever and sometimes severe disease. People living in malaria-endemic areas gradually develop resistance to symptomatic malaria and control both parasite numbers and the inflammatory response. We previously found that adaptive NK cells correlated with reduced parasite load and protection from symptoms. We also found that murine NK cell production of IL-10 protected mice from experimental cerebral malaria. Human NK cells can also secrete IL-10, but it is unknown what NK cell subsets produce IL-10 or if this is affected by malaria experience. We hypothesized that NK cell immunoregulation may lower inflammation and reduce fever induction. Here, we showed that NK cells from participants with malaria experience make significantly more IL-10 than participants with no malaria experience. We then determined the proportions of NK cells that are cytotoxic and produce IFN-γ and/or IL-10 and identified a signature of adaptive and checkpoint molecules on IL-10-producing NK cells. Lastly, we found that coculture with primary monocytes, Plasmodium-infected RBCs, and antibody induced IL-10 production by NK cells. These data suggest that NK cells may contribute to protection from malaria symptoms via IL-10 production.
恶性疟原虫感染可引发高水平炎症，导致发热，有时还会引发严重疾病。生活在疟疾流行地区的人们会逐渐对有症状的疟疾产生抵抗力，并控制寄生虫数量和炎症反应。我们之前发现，适应性自然杀伤细胞（NK细胞）与寄生虫载量降低以及免受症状影响有关。我们还发现，小鼠NK细胞产生的白细胞介素-10（IL-10）可保护小鼠免受实验性脑型疟疾的侵害。人类NK细胞也能分泌IL-10，但尚不清楚哪些NK细胞亚群产生IL-10，以及这是否受疟疾经历的影响。我们推测，NK细胞的免疫调节作用可能会减轻炎症并减少发热诱导。在此，我们发现，有疟疾经历的参与者的NK细胞产生的IL-10明显多于没有疟疾经历的参与者。然后，我们确定了具有细胞毒性并产生干扰素-γ（IFN-γ）和/或IL-10的NK细胞比例，并确定了产生IL-10的NK细胞上适应性分子和检查点分子的特征。最后，我们发现与原代单核细胞、感染疟原虫的红细胞共培养以及抗体可诱导NK细胞产生IL-10。这些数据表明，NK细胞可能通过产生IL-10有助于预防疟疾症状。
