The Drosophila CD36 Homologue croquemort Is Required to Maintain Immune and Gut Homeostasis during Development and Aging

Abstract

Phagocytosis is an ancient mechanism central to both tissue homeostasis and immune defense. Both the identity of the receptors that mediate bacterial phagocytosis and the nature of the interactions between phagocytosis and other defense mechanisms remain elusive. Here, we report that Croquemort (Crq), a Drosophila member of the CD36 family of scavenger receptors, is required for microbial phagocytosis and efficient bacterial clearance. Flies mutant for crq are susceptible to environmental microbes during development and succumb to a variety of microbial infections as adults. Crq acts parallel to the Toll and Imd pathways to eliminate bacteria via phagocytosis. crq mutant flies exhibit enhanced and prolonged immune and cytokine induction accompanied by premature gut dysplasia and decreased lifespan. The chronic state of immune activation in crq mutant flies is further regulated by negative regulators of the Imd pathway. Altogether, our data demonstrate that Crq plays a key role in maintaining immune and organismal homeostasis.

Stochastic variation in the initial phase of bacterial infection predicts the probability of survival in D. melanogaster

“…In contrast, our study indicates that the timing and intensity of AMP production is the most crucial factor for controlling bacterial infection in Drosophila . One intriguing hypothesis for reconciling the two observations is that adult Drosophila have only a small number of hemocytes due to loss of hemocytes upon aging ( Guillou et al, 2016 ), while this might not be the case in Tenebrio . Thus, the relative importance of cellular versus humoral immunity may differ between the two insects.…”

The Toll pathway underlies host sexual dimorphism in resistance to both Gram-negative and Gram-positive bacteria in mated Drosophila

“…In order to quantify hemocytes, Hml-Gal4 > UAS-GFP , eater-nlsGFP , and Pxn-Gal4 > UAS-GFP flies were decapitated and injected with sterile PBS (Nanoject II; Drummond) to detach sessile phagocytes from the tissues. Groups of 5 or 15 same-sex flies were then bled onto a glass slide, which was imaged on a Zeiss microscope (axioplot imager Zeiss) [ 49 ]. For each slide, the number of phagocytes per 25 mm 2 was counted using Zeiss’ Zen software.…”

Convergence of longevity and immunity: lessons from animal models

“…In healthy flies, susceptibility to infection increases with age as seen by measurements of antimicrobial peptide gene induction and host survival. When the phagocytic receptor croquemort is missing, flies are exposed to chronic IMD activity leading to a reduced lifespan (Guillou et al 2016 ). Moreover, there is an age-dependent decline of phagocytic ability as well as impairment in the processing of phagocytosed vesicles in older flies indicating an immunosenescent phenotype in older flies (Mackenzie et al 2011 ; Horn et al 2014 ).…”