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

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 inf...

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Autores principales: Yang, Jing, Schleicher, Tyler R., Dong, Yuemei, Park, Hyun Bong, Lan, Jiangfeng, Cresswell, Peter, Crawford, Jason, Dimopoulos, George, Fikrig, Erol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037243/
https://www.ncbi.nlm.nih.gov/pubmed/31658986
http://dx.doi.org/10.1084/jem.20190682
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author Yang, Jing
Schleicher, Tyler R.
Dong, Yuemei
Park, Hyun Bong
Lan, Jiangfeng
Cresswell, Peter
Crawford, Jason
Dimopoulos, George
Fikrig, Erol
author_facet Yang, Jing
Schleicher, Tyler R.
Dong, Yuemei
Park, Hyun Bong
Lan, Jiangfeng
Cresswell, Peter
Crawford, Jason
Dimopoulos, George
Fikrig, Erol
author_sort Yang, Jing
collection PubMed
description 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.
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spelling pubmed-70372432020-07-06 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 J Exp Med Research Articles 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. Rockefeller University Press 2019-10-28 /pmc/articles/PMC7037243/ /pubmed/31658986 http://dx.doi.org/10.1084/jem.20190682 Text en © 2019 Yang et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
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
title Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection
title_full Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection
title_fullStr Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection
title_full_unstemmed Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection
title_short Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection
title_sort disruption of mosgilt in anopheles gambiae impairs ovarian development and plasmodium infection
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037243/
https://www.ncbi.nlm.nih.gov/pubmed/31658986
http://dx.doi.org/10.1084/jem.20190682
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