Dolan Brady, Correa Gaviria Tomás, Dong Yuemei, Cresswell Peter, Dimopoulos George, Chuang Yu-Min, Fikrig Erol
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
Nat Commun. 2025 Jan 11;16(1):592. doi: 10.1038/s41467-025-55902-1.
Plasmodium, the causative agents of malaria, are obtained by mosquitoes from an infected human. Following Plasmodium acquisition by Anopheles gambiae, mosquito gamma-interferon-inducible lysosomal thiol reductase (mosGILT) plays a critical role in its subsequent sporogony in the mosquito. A critical location for this development is the midgut, a tissue we show expresses mosGILT. Using membrane-feeding and murine infection models, we demonstrate that antibodies against mosGILT reduce the number of P. falciparum and P. berghei oocysts in the midgut and the infection prevalence of both species in the mosquito. mosGILT antibodies act in the mosquito midgut, specifically impacting the Plasmodium oocyst stage. Targeting mosGILT can therefore interfere with the Plasmodium life cycle in the mosquito and potentially serve as a transmission-blocking vaccine.
疟原虫是疟疾的病原体，由蚊子从受感染的人类身上获取。冈比亚按蚊获取疟原虫后，蚊子γ干扰素诱导的溶酶体硫醇还原酶（mosGILT）在其随后在蚊子体内的孢子生殖过程中起关键作用。这一发育过程的关键部位是中肠，我们发现该组织表达mosGILT。使用膜饲法和小鼠感染模型，我们证明抗mosGILT抗体可减少中肠中恶性疟原虫和伯氏疟原虫卵囊的数量以及这两种疟原虫在蚊子中的感染率。mosGILT抗体作用于蚊子中肠，特别影响疟原虫卵囊阶段。因此，靶向mosGILT可干扰疟原虫在蚊子体内的生命周期，并有可能用作传播阻断疫苗。
