title: The JNK pathway is a key mediator of Anopheles gambiae antiplasmodial immunity.
abstract: 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.
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Lindsey S
authors.initials: LS
authors.lastname: Garver
authors.forename: Giselle
authors.initials: G
authors.lastname: de Almeida Oliveira
authors.forename: Carolina
authors.initials: C
authors.lastname: Barillas-Mury
mesh_terms: D000818:Animals; D000852:Anopheles / Q000276:immunology* / Q000469:parasitology; D019476:Insect Proteins / Q000276:immunology*; D048670:MAP Kinase Kinase 4 / Q000276:immunology*; D019255:NADPH Oxidases / Q000276:immunology; D010962:Plasmodium berghei / Q000276:immunology*; D016760:Proto-Oncogene Proteins c-fos / Q000276:immunology; D016755:Proto-Oncogene Proteins c-jun / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D019476:Insect Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D019255:NADPH Oxidases; D048670:MAP Kinase Kinase 4
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