S. Garver, Lindsey de Almeida Oliveira, Giselle Barillas-Mury, Carolina The JNK Pathway Is a Key Mediator of <i>Anopheles gambiae</i> Antiplasmodial Immunity <div><p>The innate immune system of <i>Anopheles gambiae</i> mosquitoes limits <i>Plasmodium</i> 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 <i>Hep</i>, <i>JNK</i>, <i>Jun</i> or <i>Fos</i> expression, greatly enhanced <i>Plasmodium</i> infection; while overactivating this cascade, by silencing the suppressor <i>Puckered</i>, 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 <i>Plasmodium</i> infection and regulates expression of two key hemocyte-derived immune effectors (TEP1 and FBN9). Furthermore, the <i>An. gambiae</i> L3–5 strain that has been genetically selected to be refractory (R) to <i>Plasmodium</i> 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 <i>An. gambiae</i> mosquitoes to limit <i>Plasmodium</i> infection and identified several effector genes mediating these responses.</p></div> microbiology;Vector biology;mosquitoes;Infectious diseases;Vectors and hosts;jnk;pathway;mediator;antiplasmodial;immunity 2013-09-05