The role of detoxification in the mosquito Anopheles gambiae response to Plasmodium infection

Background: Anopheles 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. Results: Using 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. Conclusions: Most 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. Background The mosquito Anopheles gambiae is the main malaria vector in sub-Saharan Africa. 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 mosquito becomes infected with the malaria parasite by taking a blood meal. 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]. These products may represent potential oxidative stress that can be ameliorated or eliminated by detoxification enzymes. For example several glutathione Stransferases (GSTs) have peroxidase activity and some can also metabolise reactive a,b-aldehydes [4]. GST expression can also be induced by reactive oxygen species (ROS) [5,6]. While GSTs help to eliminate ROS, cytochrome P450 monooxygenases (CYP) may actually contribute towards its generation [7]. Although transcription alteration of detoxification genes in response to bacteria and Plasmodium [8-10] has been described, the nature of this response hasn’t been fully discussed. In this study we describe the impact of P. berghei infection at two time points (1 day and 11 days post infection) on the expression of detoxification genes in the midgut and fat body. We identified several genes, previously implicated in the detoxification of xenobiotics, which are differentially expressed in relation to parasite infection in the midgut and fat body. * Correspondence: hsilveira@ihmt.unl. pt Centro de Malária e Outras Doenças Tropicais, UEI Malária, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira, 96, 1349-008 Lisbon, Portugal Félix et al. BMC Genomics 2010, 11:312 http://www.biomedcentral. com/1471-2164/11/312 © 2010 Félix et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.