Proteomic analysis of the Anopheles gambiae response to a Plasmodium berghei infection
Institution:
StrasbourgDisciplines:
Directors:
Abstract EN:
Malaria is a mosquito-borne infectious disease yearly affecting an estimated 500 million humans, of which 1 to 2 million (mostly children in Sub-Saharan Africa) succumb to the disease. Malaria transmission is initiated when a female mosquito ingests gametocytes during a blood meal, required for ovary development. Thus, feeding on a malaria-infected host will simultaneously activate oogenesis and allow malaria parasites to invade mosquito tissues. However, the parasites undergo massive losses during their development in the vector, due to the powerful immune response that mosquitoes mount against the invading parasites. The basis of this antiparasitic response has been investigated previously using reverse genetic approaches and has identified several antiparasitic molecules including TEP1, a homologue of vertebrate complement factor C3, which mediates parasite killing in a complement-like manner. However, additional mosquito factors involved in this killing mechanism including effector molecules are yet to be identified. To this aim, transgenic mosquitoes with TEP1 gain-of-function (GOF) and loss-of-function (LOF) were established, and transcriptional analysis of their immune response during parasite development performed as a basis for examining the pathway. Because transcript levels do not always correlate with protein abundance, we complemented the microarray analysis with a proteomic analysis of the mosquito response towards a Plasmodium berghei infection in the midgut tissues. […]
Abstract FR:
L’anophèle, vecteur du paludisme chez l’homme, acquiert le Plasmodium au cours du repas sanguin. Sa réponse immunitaire s’oppose à l’invasion du parasite. TEP1 est un facteur antiparasitaire homologue au facteur C3 du complément. Pour étudier la réponse antiparasitaire TEP1-dépendante, nous avons entrepris une analyse protéomique sur intestins de moustiques transgéniques infectés et présentons les protéines identifiées. Nous avons montré que la Lipophorine et la Vitellogénine, protéines fournissant des nutriments aux ovocytes en développement, influencent la réponse antiparasitaire en réduisant l’efficacité antiparasitaire de TEP1. De plus, les facteurs de transcription Cactus/Rel1-Rel2, contrôlant l’expression de facteurs immunitaires, régulent également l’expression de la vitellogénine. Ces résultats mettent en évidence des liens multiples entre reproduction et immunité, établissant une base moléculaire aux interactions soupçonnées entre ces processus.