Abstract
The malarial parasite Plasmodium must complete a complex lifecycle in its Anopheles mosquito host, the main vector for Plasmodium. The mosquito resists infection with the human malarial parasite P. falciparum by engaging the NF-κB immune signaling pathway, IMD. Here we show that the conserved transcriptional mediators Kto and Skd are involved in the regulation of the mosquito IMD pathway. RNAi-mediated depletion of Kto and Skd in the Anopheles gambiae cell line L5-3 resulted in a decrease in the transcript abundance of Cec1, which is controlled by the IMD pathway. Silencing the two genes also resulted in an increased susceptibility of the mosquito to bacterial and Plasmodium falciparum infection, but not to infection with the rodent malaria parasite P. berghei. We also showed that Kto and Skd are not transcriptional co-activators of Rel2 or other key factors of the IMD pathway; however, they participate in the regulation of the IMD pathway, which is crucial for the mosquito’s defense against P. falciparum.
Highlights
Malaria, one of the deadliest diseases in the world, is responsible for the deaths of over one million people annually
Kto Regulates the IMD Pathway In order to determine the role of Kto in the regulation of the IMD pathway, we monitored the activation of the immune pathway after using RNAi to silence the expression of Kto in the L3-5 mosquito cell line [31], which expresses firefly luciferase under a IMD pathway-regulated Cec1 promoter
We have shown for the first time that Kto and Skd play key roles in regulating the IMD pathway in the mosquito, an essential part of the innate immune system’s defense against bacterial and P. falciparum infections
Summary
One of the deadliest diseases in the world, is responsible for the deaths of over one million people annually. Anopheles mosquitoes are the main vectors for protozoan parasites of the genus Plasmodium, which cause the disease. The innate immune system of the mosquito is the main defense against the Plasmodium parasites [1,2,3,4]. A better understanding of the interaction between the parasite and the mosquito’s immune system could facilitate the development of novel disease control and prevention strategies. Several anti-Plasmodium immune effectors controlled by the IMD pathway, such as TEP1, APL1, LRRD7 and FBN9, have been characterized with regard to their anti-parasitic activity [3,7,8,9,10,11,12,13]
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