Malaria mosquito antimicrobial defence requires immunity and detoxification gene regulation by Lola

Malaria-causing Plasmodium parasites are transmitted by some Anopheles mosquito species. The genetic and immunity basis for vector competence, the mosquitoes' intrinsic ability to transmit pathogens, has been extensively studied in major vectors such as Anopheles gambiae and Anopeles stephensi. In An. gambiae, Lola-type motifs were identified in immunity-related cis-regulatory elements; the Lola transcription factor is known to be involved in Drosophila development. Here, the potential role of lola in mosquito antimicrobial defence was investigated in Anopheles albimanus, a malaria vector in the Americas. The in vivo attenuation of lola was found to compromise mosquito survival to microbial infection. It was also found that the induction of antimicrobial defence genes requires lola upregulation. Genes for antimicrobial peptides, C-lectins, pattern recognition receptors, Clip-domain serine proteases and ML-domain proteins showed lola upregulation dependency. Enzymes involved in the generation and detoxification of reactive oxygen species, as well as components of the JNK immune signalling pathways, are also dependent on lola upregulation. These findings suggest that lola regulates the expression of immunity and detoxification genes and that there is a functional link between JNK signalling and lola expression in the mosquito midgut. Dysregulation of this pathway may contribute to increased pathogen invasion and malaria transmission.