Elimination of plasmatocytes by targeted apoptosis reveals their role in multiple aspects of the Drosophila immune response

Abstract

Drosophila hemocytes have strong phagocytic capacities and produce antimicrobial peptides (AMPs). However, the precise role of blood cells during immune responses and developmental processes has only been studied using indirect means. To overcome this limitation, we generated plasmatocyte-depleted flies by specifically overexpressing the proapoptotic protein Hid into plasmatocytes. Unexpectedly, these plasmatocyte-depleted animals have a normal larval and pupal development and do not exhibit any obvious defect after birth. Remarkably, plasmatocyte-depleted adults show a strong susceptibility to infections by various microorganisms, although activation of systemic AMP gene transcription via the Toll and immune deficiency (IMD) pathways is wild-type. Our data show that this susceptibility, which correlates with overproliferation of bacteria, is likely due to the absence of phagocytosis. We also demonstrate that during larval stages, plasmatocytes play an essential role in mediating AMP production by the fat body after oral bacterial infection. Finally, we show that plasmatocytes are involved in immune surveillance during pupal development, because they prevent bacterial infection that causes pupal lethality.AMP ͉ blood cells ͉ innate immunity ͉ Toll

Methods to study Drosophila immunity

“…Viable flies lacking all or most plasmatocytes are called phagoless and can be generated by crossing a hemocyte gal4 driver (Hml-Gal4 or spn-Gal4) to either uas-Bax or both uashid and uas-rpr [53,54].…”

“…Hemocyte drivers and markers w 1118 ; P{Hml-GAL4.D}2, P{UAS-2xEGFP}AH2 BL30140 [53,54] This GAL4 line expresses in all the plasmatocytes. Note that this line is deleted for NimC1 gene [133].…”

Structural and functional characterization of pseudopodocyte, a shaggy immune cell produced by two Drosophila species of the obscura group

“…Their cytoplasm encloses a well-developed Golgi apparatus, a rough endoplasmic reticulum (RER) developed in large cisternae, numerous free ribosomes, lipidic vesicles, and phagolysosome-like inclusions (Ribeiro and Brehélin, 2006). Plasmatocytes are involved in phagocytosis, wound healing, production of antimicrobial peptides and, probably, in foreign body recognition, too (Brehélin, 1982;Franc et al, 1999;Ribeiro and Brehélin, 2006;Samakovlis et al, 1990;Dimarcq, 1997;Tzou et al, 2002;Meister, 2004;Charoux and Royet, 2009). They also contribute to encapsulation: they were shown attaching to the chorion of a parasitoid egg within a few hours after parasitization, thus being the first cells to come in contact with the foreign body at the very beginning of capsule formation (Russo et al, 1996;Williams et al, 2005).…”

Recognition of Pathogenic Microbes by the Drosophila Phagocytic Pattern Recognition Receptor Eater

“…These Drosophila phagocytes are long-lived (7,8) and devoid of neutrophil-like granules (9,10). They play essential roles in tissue remodeling during development (11) and in immunity during infection (11)(12)(13)(14).…”

“…Our laboratory identified Eater, a receptor expressed by S2 cells and primary hemocytes (15). Eater plays a critical, non-redundant role in host survival after bacterial infections (11,13,15,16). 2 Flies lacking the eater gene display impaired phagocytosis and increased bacterial loads yet intact immune signaling via the NFB-like pathways Toll and Imd (15,16).…”