Reactive Oxygen Species-Dependent Cell Signaling Regulates the Mosquito Immune Response to Plasmodium falciparum

Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California 95616, USA.
Antioxidants & Redox Signaling (Impact Factor: 7.67). 03/2011; 14(6):943-55. DOI: 10.1089/ars.2010.3401
Source: PubMed

ABSTRACT Reactive oxygen species (ROS) have been implicated in direct killing of pathogens, increased tissue damage, and regulation of immune signaling pathways in mammalian cells. Available research suggests that analogous phenomena affect the establishment of Plasmodium infection in Anopheles mosquitoes. We have previously shown that provision of human insulin in a blood meal leads to increased ROS levels in Anopheles stephensi. Here, we demonstrate that provision of human insulin significantly increased parasite development in the same mosquito host in a manner that was not consistent with ROS-induced parasite killing or parasite escape through damaged tissue. Rather, our studies demonstrate that ROS are important mediators of both the mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signaling branches of the mosquito insulin signaling cascade. Further, ROS alone can directly activate these signaling pathways and this activation is growth factor specific. Our data, therefore, highlight a novel role for ROS as signaling mediators in the mosquito innate immune response to Plasmodium parasites.

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    PLoS Pathogens 06/2014; 10(6):e1004231. DOI:10.1371/journal.ppat.1004231 · 8.14 Impact Factor
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    ABSTRACT: With increasing prevalence rates of diabetes mellitus in tropical countries, malaria and diabetes often coincide. The study was designed to investigate the effects of glucose and insulin upon in vitro proliferation of Plasmodium falciparum, the causative agent of malaria tropica. Plasmodium falciparum proliferation was determined via the Malstat™ assay, following incubation of the parasites at varying concentrations of glucose (0 -27.7mM) or insulin (10 pM -100µM) for 24 and 48 hrs. While Plasmodium falciparum proliferation was unaffected at concentrations of 5.5 – 27.7mM glucose, growth w as impaired below a threshold of 5.5mM. No effect was seen following incubation of the parasites in the presence of 10pM – 100µM insulin. Insulin levels did not affect parasite proliferation whilst glucose levels below 5.5mM reduced parasite growth. The Malstat™ assay was identified as a suitable screening assay to assess the effects of glycemic control upon Plasmodium falciparum growth.

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Jun 10, 2014