Work

AP-1/Fos-TGase2 Axis Mediates Wounding-induced Plasmodium falciparum Killing in Anopheles gambiae

Year: 2013

Type: article

Abstract: Anopheline mosquitoes are the only vectors of human malaria worldwide. It is now widely accepted that mosquito immune responses play a crucial role in restricting Plasmodium development within the vector; therefore, further dissection of the molecular mechanisms underlying these processes should inform new vector control strategies urgently needed to roll back the disease. Here, using genome-wide transcriptional profiling, bioinformatics, and functional gene analysis, we identify a new axis of mosquito resistance to monoclonal Plasmodium falciparum infections that includes the AP-1 transcription factor Fos and the transglutaminase 2 (TGase2), a cross-linking enzyme with known roles in wound responses. We demonstrate that Fos regulates induction of TGase2 expression after wounding but does not affect expression of the components of the well characterized complement-like system. Silencing of Fos or of TGase2 aborts the wounding-induced mosquito killing of P. falciparum . These results reveal multiple signaling pathways that are required for efficient Plasmodium killing in Anopheles gambiae. Background: Wounding renders mosquitoes resistant to human malaria parasites. Results: Genome-wide transcriptional profiling identified 53 wound response genes, including two transglutaminases. Functional studies revealed the role of AP-1/TGase2 axis in the mosquito resistance to Plasmodium falciparum . Conclusion: AP-1/TGase2 is a new axis of the mosquito immune responses to malaria parasites. Significance: Multiple signaling pathways contribute to mosquito resistance to malaria and represent new potential targets for vector control interventions.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m112.443267