Reactive Oxygen Species Modulate Anopheles gambiae Immunity against Bacteria and Plasmodium

Abstract

The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. Strains of An. gambiae with higher systemic levels of ROS survive a bacterial challenge better, whereas reduction of ROS by dietary administration of antioxidants significantly decreases survival, indicating that ROS are required to mount effective antibacterial responses. Expression of several ROS detoxification enzymes increases in the midgut and fat body after a blood meal. Furthermore, expression of several of these enzymes increases to even higher levels when mosquitoes are fed a Plasmodium berghei-infected meal, indicating that the oxidative stress after a blood meal is exacerbated by Plasmodium infection. Paradoxically, a complete lack of induction of catalase mRNA and lower catalase activity were observed in P. berghei-infected midguts. This suppression of midgut catalase expression is a specific response to ookinete midgut invasion and is expected to lead to higher local levels of hydrogen peroxide. Further reduction of catalase expression by double-stranded RNA-mediated gene silencing promoted parasite clearance by a lytic mechanism and reduced infection significantly. High mosquito mortality is often observed after P. berghei infection. Death appears to result in part from excess production of ROS, as mortality can be decreased by oral administration of uric acid, a strong antioxidant. We conclude that ROS modulate An. gambiae immunity and that the mosquito response to P. berghei involves a local reduction of detoxification of hydrogen peroxide in the midgut that contributes to limit Plasmodium infection through a lytic mechanism.

Insecticide exposure impacts vector–parasite interactions in insecticide-resistant malaria vectors

“…Indeed, insecticides modulate the expression of several genes, particularly those related to xenobiotic detoxification and mitochondrial redox metabolism [30], and increased cytochromes P450 expression which are known to amplify the oxidative stress [31]. This may interfere with parasite development as oxidative stress induced by blood meal, and Plasmodium ingestion was shown to play critical role in controlling the infection [32,33]. Although our experimental design did not allow testing for oxidative stress induced by insecticide exposure; we may conjecture that insecticides prevent Plasmodium development through higher reactive oxygen species level and increased cytochrome P450 expression.…”

Some strains of Plasmodium falciparum , a human malaria parasite, evade the complement-like system of Anopheles gambiae mosquitoes

“…Individual female A. gambiae mosquitoes were injected 1-2 d postemergence as previously described (24). Briefly, mosquitoes were injected with 69 nL 3 μg/μL dsRNA solution 3-4 d before receiving a Plasmodium-infected blood meal.…”

Intruders below the Radar: Molecular Pathogenesis of Bartonella spp

“…Most obviously, such a surface coat would provide a nutritive reservoir for Bartonella, especially as it has to compete with its arthropod vector for heme in the midgut (25). Furthermore, the intrinsic peroxidase activity of heme would make the coat a potent antioxidant barrier (25) and hence constitute a suitable protectant against reactive oxygen species (ROS) as key mediators of antimicrobial defense both in the arthropod gut (169,305) and as part of mammal immune defenses (42). ROS release in the arthropod gut is highly regulated, for example, in order to protect symbionts (168), and was found to be decreased in bloodsucking arthropods upon perception of heme in the gut lumen (319).…”