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The JNK Pathway Is a Key Mediator of Anopheles gambiae Antiplasmodial Immunity
The innate immune system of Anopheles gambiae mosquitoes limits Plasmodium infection through multiple molecular mechanisms. For example, midgut invasion by the parasite triggers an epithelial nitration response that promotes activation of the complement-like system. We found that suppression of the...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764222/ https://www.ncbi.nlm.nih.gov/pubmed/24039583 http://dx.doi.org/10.1371/journal.ppat.1003622 |
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author | Garver, Lindsey S. de Almeida Oliveira, Giselle Barillas-Mury, Carolina |
author_facet | Garver, Lindsey S. de Almeida Oliveira, Giselle Barillas-Mury, Carolina |
author_sort | Garver, Lindsey S. |
collection | PubMed |
description | The innate immune system of Anopheles gambiae mosquitoes limits Plasmodium infection through multiple molecular mechanisms. For example, midgut invasion by the parasite triggers an epithelial nitration response that promotes activation of the complement-like system. We found that suppression of the JNK pathway, by silencing either Hep, JNK, Jun or Fos expression, greatly enhanced Plasmodium infection; while overactivating this cascade, by silencing the suppressor Puckered, had the opposite effect. The JNK pathway limits infection via two coordinated responses. It induces the expression of two enzymes (HPx2 and NOX5) that potentiate midgut epithelial nitration in response to Plasmodium infection and regulates expression of two key hemocyte-derived immune effectors (TEP1 and FBN9). Furthermore, the An. gambiae L3–5 strain that has been genetically selected to be refractory (R) to Plasmodium infection exhibits constitutive overexpression of genes from the JNK pathway, as well as midgut and hemocyte effector genes. Silencing experiments confirmed that this cascade mediates, to a large extent, the drastic parasite elimination phenotype characteristic of this mosquito strain. In sum, these studies revealed the JNK pathway as a key regulator of the ability of An. gambiae mosquitoes to limit Plasmodium infection and identified several effector genes mediating these responses. |
format | Online Article Text |
id | pubmed-3764222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37642222013-09-13 The JNK Pathway Is a Key Mediator of Anopheles gambiae Antiplasmodial Immunity Garver, Lindsey S. de Almeida Oliveira, Giselle Barillas-Mury, Carolina PLoS Pathog Research Article The innate immune system of Anopheles gambiae mosquitoes limits Plasmodium infection through multiple molecular mechanisms. For example, midgut invasion by the parasite triggers an epithelial nitration response that promotes activation of the complement-like system. We found that suppression of the JNK pathway, by silencing either Hep, JNK, Jun or Fos expression, greatly enhanced Plasmodium infection; while overactivating this cascade, by silencing the suppressor Puckered, had the opposite effect. The JNK pathway limits infection via two coordinated responses. It induces the expression of two enzymes (HPx2 and NOX5) that potentiate midgut epithelial nitration in response to Plasmodium infection and regulates expression of two key hemocyte-derived immune effectors (TEP1 and FBN9). Furthermore, the An. gambiae L3–5 strain that has been genetically selected to be refractory (R) to Plasmodium infection exhibits constitutive overexpression of genes from the JNK pathway, as well as midgut and hemocyte effector genes. Silencing experiments confirmed that this cascade mediates, to a large extent, the drastic parasite elimination phenotype characteristic of this mosquito strain. In sum, these studies revealed the JNK pathway as a key regulator of the ability of An. gambiae mosquitoes to limit Plasmodium infection and identified several effector genes mediating these responses. Public Library of Science 2013-09-05 /pmc/articles/PMC3764222/ /pubmed/24039583 http://dx.doi.org/10.1371/journal.ppat.1003622 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Garver, Lindsey S. de Almeida Oliveira, Giselle Barillas-Mury, Carolina The JNK Pathway Is a Key Mediator of Anopheles gambiae Antiplasmodial Immunity |
title | The JNK Pathway Is a Key Mediator of Anopheles gambiae Antiplasmodial Immunity |
title_full | The JNK Pathway Is a Key Mediator of Anopheles gambiae Antiplasmodial Immunity |
title_fullStr | The JNK Pathway Is a Key Mediator of Anopheles gambiae Antiplasmodial Immunity |
title_full_unstemmed | The JNK Pathway Is a Key Mediator of Anopheles gambiae Antiplasmodial Immunity |
title_short | The JNK Pathway Is a Key Mediator of Anopheles gambiae Antiplasmodial Immunity |
title_sort | jnk pathway is a key mediator of anopheles gambiae antiplasmodial immunity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764222/ https://www.ncbi.nlm.nih.gov/pubmed/24039583 http://dx.doi.org/10.1371/journal.ppat.1003622 |
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