Plasmodium infection alters Anopheles gambiae detoxification gene expression

Rute C Félix,Pie Müller,Henrique Silveira,Vera Ribeiro,Hilary Ranson

doi:10.1186/1471-2164-11-312

Abstract

BackgroundAnopheles gambiae has been shown to change its global gene expression patterns upon Plasmodium infection. While many alterations are directly related to the mosquito's innate immune response, parasite invasion is also expected to generate toxic by-products such as free radicals. The current study aimed at identifying which loci coding for detoxification enzymes are differentially expressed as a function of Plasmodium berghei infection in midgut and fat body tissues.ResultsUsing a custom-made DNA microarray, transcript levels of 254 loci primarily belonging to three major detoxification enzyme families (glutathione S-transferases, cytochrome P450 monooxygenases and esterases) were compared in infected and uninfected mosquitoes both during ookinete invasion and the release of sporozoites into the hemocoel. The greatest changes in gene expression were observed in the midgut in response to ookinete invasion. Interestingly, many detoxification genes including a large number of P450s were down-regulated at this stage. In the fat body, while less dramatic, gene expression alterations were also observed and occurred during the ookinete invasion and during the release of sporozoites into the hemocoel. While most gene expression changes were tissue-related, CYP6M2, a CYP previously associated with insecticide resistance, was over-expressed both in the midgut and fat body during ookinete invasion.ConclusionsMost toxicity-related reactions occur in the midgut shortly after the ingestion of an infected blood meal. Strong up-regulation of CYP6M2 in the midgut and the fat body as well as its previous association with insecticide resistance shows its broad role in metabolic detoxification.

Highlights

Anopheles gambiae has been shown to change its global gene expression patterns upon Plasmodium infection
Microarray Tissues for microarray analyses were collected at two critical time points of the Plasmodium cycle in the mosquito host: 1 day following the blood meal, during which parasites invade the midgut epithelium, and 11 days after the blood meal when sporozoites are starting to be released to the hemolymph, as demonstrated by detection of parasite’s DNA in the hemolymph
The microarray experiment was developed to answer the following questions, regarding midgut and fat body tissues: 1. which genes respond to Plasmodium midgut epithelium invasion (1 day post blood meal) 2. which genes respond to the release of sporozoites into the hemolymph (11 days post blood meal), and 3. which genes respond differently between the two events

Summary

Introduction

Anopheles gambiae has been shown to change its global gene expression patterns upon Plasmodium infection. Resistance to anti-malaria drugs and insecticides together with the lack of vaccines highlight the need for novel strategies in malaria control Such a strategy could be the interruption of the transmission cycle within the mosquito. The blood meal itself brings metabolic changes and induces a state of oxidative stress [1,2]. This is further increased by the presence of Plasmodium parasites in the blood meal [3]. During mosquito response to infection, active nitrogen and oxygen radicals are produced to contain Plasmodium infection [1,3].

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