Regulation of Anti-<em>Plasmodium</em> Immunity by a <em>LITAF</em>-like Transcription Factor in the Malaria Vector <em>Anopheles gambiae</em>

<div><p>The mosquito is the obligate vector for malaria transmission. To complete its development within the mosquito, the malaria parasite <em>Plasmodium</em> must overcome the protective action of the mosquito innate immune system. Here we report on the involvement of the <em>Anopheles gambiae</em> orthologue of a conserved component of the vertebrate immune system, LPS-induced TNFα transcription factor (<em>LITAF</em>), and its role in mosquito anti-<em>Plasmodium</em> immunity. <em>An. gambiae LITAF</em>-like 3 (<em>LL3</em>) expression is up-regulated in response to midgut invasion by both rodent and human malaria parasites. Silencing of <em>LL3</em> expression greatly increases parasite survival, indicating that <em>LL3</em> is part of an anti-<em>Plasmodium</em> defense mechanism. Electrophoretic mobility shift assays identified specific LL3 DNA-binding motifs within the promoter of <em>SRPN6</em>, a gene that also mediates mosquito defense against <em>Plasmodium</em>. Further experiments indicated that these motifs play a direct role in LL3 regulation of <em>SRPN6</em> expression. We conclude that <em>LL3</em> is a transcription factor capable of modulating <em>SRPN6</em> expression as part of the mosquito anti-<em>Plasmodium</em> immune response.</p>