The raspberry Gene Is Involved in the Regulation of the Cellular Immune Response in Drosophila melanogaster

Abstract

Drosophila is an extremely useful model organism for understanding how innate immune mechanisms defend against microbes and parasitoids. Large foreign objects trigger a potent cellular immune response in Drosophila larva. In the case of endoparasitoid wasp eggs, this response includes hemocyte proliferation, lamellocyte differentiation and eventual encapsulation of the egg. The encapsulation reaction involves the attachment and spreading of hemocytes around the egg, which requires cytoskeletal rearrangements, changes in adhesion properties and cell shape, as well as melanization of the capsule. Guanine nucleotide metabolism has an essential role in the regulation of pathways necessary for this encapsulation response. Here, we show that the Drosophila inosine 5'-monophosphate dehydrogenase (IMPDH), encoded by raspberry (ras), is centrally important for a proper cellular immune response against eggs from the parasitoid wasp Leptopilina boulardi. Notably, hemocyte attachment to the egg and subsequent melanization of the capsule are deficient in hypomorphic ras mutant larvae, which results in a compromised cellular immune response and increased survival of the parasitoid.

Embryonic hematopoiesis modulates the inflammatory response and larval hematopoiesis in Drosophila

“…Wasp parasitization by L. Boulardi is commonly used to study the immune response of Drosophila ( Yang et al, 2015 ; Small et al, 2012 ; Vanha-Aho et al, 2015 ; Kari et al, 2016 ). The wasp lays eggs in the Drosophila larva, which induces a strong systemic inflammatory cascade that leads to the differentiation of plasmatocytes into lamellocytes and to the encapsulation of the wasp egg ( Small et al, 2012 ).…”

A novel mode of induction of the humoral innate immune response in Drosophila larvae

“…These play central roles in cellular immunity by phagocytosing bacteria (plasmatocytes), involvement in the melanization process (crystal cells) and forming capsules around wasp eggs, a process referred to as encapsulation (lamellocytes) ( Honti et al, 2014 ; Gold and Brückner, 2015 ; Parsons and Foley, 2016 ). For example, recent studies have begun to unravel the complex encapsulation processes by using Drosophila larvae upon infection with parasitoid wasps such as Leptopilina boulardi ( Kari et al, 2016 ). In addition, the fat body, an immune-responsive organ in flies functionally resembling the mammalian liver, expresses edin and utilizes Toll signaling to control the numbers of plasmatocytes ( Schmid et al, 2014 ; Vanha-aho et al, 2015 ).…”

Extraction of Hemocytes from <em>Drosophila melanogaster</em> Larvae for Microbial Infection and Analysis

“…Additionally, for the ex vivo infections presented here, a large number of hemocytes are needed. To avoid melanization 31,32,33 , dissection and hemocyte collection must occur rapidly. While other methods for hemocyte extraction exist 18,19,23 , the duration of these methods to collect a sufficiently large number of hemocytes for ex vivo infection was too long.…”

“…A common immune response in Drosophila to injury, which occurs during the opening and dissection of the larval cuticle, is melanization 31,32,33 . During the extraction of hemocytes, we would observe melanization of the hemocytes in the DHIM as early as 10 min following extraction.…”