Wu Ye, Chen Ying-Chun, Liu Fang-Fang, Li Ke
Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Department of Laboratory Medicine, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, People's Republic of China.
Immun Inflamm Dis. 2025 Feb;13(2):e70148. doi: 10.1002/iid3.70148.
Malaria remains a significant global health challenge, with substantial mortality rates, particularly in tropical and subtropical regions. A notable sexual dimorphism exists in malaria, with males often experiencing higher infection and mortality rates compared to females.
This review explores the role of estrogen in modulating immune responses to malaria, potentially explaining the observed sex differences. Estrogen, through its receptors, influences immune cell activation and cytokine production, which are critical in the immune response to malaria.
Utilizing data from the Global Burden of Disease (GBD) study, we analyzed sex differences in malaria burden in Central Sub-Saharan Africa from 2000 to 2021, revealing a significantly lower mortality burden for females compared to males. Epidemiological data and animal model results support the notion that estrogen plays a significant role in modulating immune responses to malaria. Estrogen receptors are widely expressed in immune cells, and estrogen can influence the activation, proliferation, and differentiation of these cells, thereby affecting cytokine production and immune response type. Additionally, selective estrogen receptor modulators (SERMs) show potential as therapeutic agents, with some studies demonstrating their efficacy in reducing parasitemia and improving malaria outcomes.
Understanding the sex differences in the pathogenesis of malaria is crucial for its prevention, treatment, and vaccine development. Estrogen's role in immune regulation highlights the need for sex-specific approaches in disease management.
疟疾仍然是一项重大的全球卫生挑战，死亡率很高，尤其是在热带和亚热带地区。疟疾存在明显的性别差异，与女性相比，男性通常感染率和死亡率更高。
本综述探讨雌激素在调节对疟疾的免疫反应中的作用，这可能解释所观察到的性别差异。雌激素通过其受体影响免疫细胞的激活和细胞因子的产生，而这在对疟疾的免疫反应中至关重要。
利用全球疾病负担（GBD）研究的数据，我们分析了2000年至2021年撒哈拉以南非洲中部地区疟疾负担的性别差异，结果显示女性的死亡负担明显低于男性。流行病学数据和动物模型结果支持雌激素在调节对疟疾的免疫反应中起重要作用这一观点。雌激素受体在免疫细胞中广泛表达，雌激素可影响这些细胞的激活、增殖和分化，从而影响细胞因子的产生和免疫反应类型。此外，选择性雌激素受体调节剂（SERM）显示出作为治疗药物的潜力，一些研究证明了它们在降低寄生虫血症和改善疟疾结局方面的疗效。
了解疟疾发病机制中的性别差异对于其预防、治疗和疫苗开发至关重要。雌激素在免疫调节中的作用凸显了在疾病管理中采用针对性别的方法的必要性。
