The major A. gambiae defense against P. falciparum is controlled by the short isoform of the immune signalling factor Rel2, which regulates APL1A expression.

A) Gene silencing of immune signalling factors Rel1 and Rel2 is specific for the targeted genes. B) Silencing of Rel2 but not Rel1 permits significantly higher P. falciparum infection prevalence in treated mosquitoes. C) Genetic interactions between Rel2 isoforms and APL1 paralogs. dsRel2 targets a common region shared by Rel2-Short and the ankyrin-domain containing Rel2-Full transcript isoforms. dsRel2 treatment diminishes both of the Rel2 transcripts, and also specifically silences APL1A but not APL1B or APL1C (RT-PCR in the horizontal row labelled Rel2 detects both Rel2 transcripts, while the row labelled Rel2(Ank) detects only the longer Rel2-Full form). In contrast, treatment with dsRel2(Ank) efficiently diminishes the cognate long-form transcript (RT-PCR in row labelled Rel2(Ank)) and presumably the long-form proportion of the total Rel2 transcripts detected by Rel2 RT-PCR (row Rel2), but does not affect transcript levels of APL1A, APL1B, or APL1C. D) Of the Rel2 isoforms, only the short-form Rel2-S is required both for APL1A expression and for protection against P. falciparum infection. dsRel2 treatment causes significantly higher infection prevalence, with no detectable effect on oocyst intensity. dsRel2(Ank) targets only the long-form transcript, and does not affect APL1A levels nor influence parasite infection.