Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection

Jing Yang, Tyler R. Schleicher, Yuemei Dong, Hyun Bong Park, Jiangfeng Lan, Peter Cresswell, Jason Crawford, George Dimopoulos, Erol Fikrig

Research output: Contribution to journalArticle

Abstract

Plasmodium infection in Anopheles is influenced by mosquito-derived factors. We previously showed that a protein in saliva from infected Anopheles, mosquito gamma-interferon-inducible lysosomal thiol reductase (mosGILT), inhibits the ability of sporozoites to traverse cells and readily establish infection of the vertebrate host. To determine whether mosGILT influences Plasmodium within the mosquito, we generated Anopheles gambiae mosquitoes carrying mosaic mutations in the mosGILT gene using CRISPR/CRISPR associated protein 9 (Cas9). Here, we show that female mosaic mosGILT mutant mosquitoes display defects in ovarian development and refractoriness to Plasmodium. Following infection by either Plasmodium berghei or Plasmodium falciparum, mutant mosquitoes have significantly reduced oocyst numbers as a result of increased thioester-containing protein 1 (TEP1)-dependent parasite killing. Expression of vitellogenin (Vg), the major yolk protein that can reduce the parasite-killing efficiency of TEP1, is severely impaired in mutant mosquitoes. MosGILT is a mosquito factor that is essential for ovarian development and indirectly protects both human and rodent Plasmodium species from mosquito immunity.

Original languageEnglish (US)
JournalThe Journal of experimental medicine
Volume217
Issue number1
DOIs
StatePublished - Jan 6 2020

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Anopheles gambiae
Culicidae
Sulfhydryl Compounds
Malaria
Interferon-gamma
Oxidoreductases
Plasmodium
Anopheles
CRISPR-Associated Proteins
Parasites
Clustered Regularly Interspaced Short Palindromic Repeats
Vitellogenins
Egg Proteins
Plasmodium berghei
Sporozoites
Proteins
Oocysts
Plasmodium falciparum
Infection
Saliva

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection. / Yang, Jing; Schleicher, Tyler R.; Dong, Yuemei; Park, Hyun Bong; Lan, Jiangfeng; Cresswell, Peter; Crawford, Jason; Dimopoulos, George; Fikrig, Erol.

In: The Journal of experimental medicine, Vol. 217, No. 1, 06.01.2020.

Research output: Contribution to journalArticle

Yang, Jing ; Schleicher, Tyler R. ; Dong, Yuemei ; Park, Hyun Bong ; Lan, Jiangfeng ; Cresswell, Peter ; Crawford, Jason ; Dimopoulos, George ; Fikrig, Erol. / Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection. In: The Journal of experimental medicine. 2020 ; Vol. 217, No. 1.
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