Phagocytosis Is the Sole Arm of Drosophila melanogaster Known Host Defenses That Provides Some Protection Against Microsporidia Infection

Abstract

Microsporidia are obligate intracellular parasites able to infest specifically a large range of species, including insects. The knowledge about the biology of microsporidial infections remains confined to mostly descriptive studies, including molecular approaches such as transcriptomics or proteomics. Thus, functional data to understand insect host defenses are currently lacking. Here, we have undertaken a genetic analysis of known host defenses of the Drosophila melanogaster using an infection model whereby Tubulinosema ratisbonensis spores are directly injected in this insect. We find that phagocytosis does confer some protection in this infection model. In contrast, the systemic immune response, extracellular reactive oxygen species, thioester proteins, xenophagy, and intracellular antiviral response pathways do not appear to be involved in the resistance against this parasite. Unexpectedly, several genes such as PGRP-LE seem to promote this infection. The prophenol oxidases that mediate melanization have different functions; PPO1 presents a phenotype similar to that of PGRP-LE whereas that of PPO2 suggests a function in the resilience to infection. Similarly, eiger and Unpaired3, which encode two cytokines secreted by hemocytes display a resilience phenotype with a strong susceptibility to T. ratisbonensis.

TNF signaling mediates cellular immune function and promotes malaria parasite killing in the mosquitoAnopheles gambiae

“…Although TNF-α is a well-established proinflammatory cytokine known for its role in regulating various aspects of macrophage function in vertebrates [64,65], our 1 understanding of TNF signaling on insect immune cells has been limited. Previous studies have implicated Eiger/TNF in phagocytosis and host survival to pathogen infection [44][45][46], supporting the conservation of the TNF signaling pathway across insect taxa. Moreover, TNF signaling has been implicated in regulating phagocytic immune cell populations in solitary locusts [46] and in promoting crystal cell rupture in Drosophila [42].…”

“…With the Drosophila TNF pathway comprising an analogous TNF ligand, Eiger, and the receptors, Wengen (Wgn) and Grindelwald (Grnd) [37], Drosophila TNF signaling regulates several physiological processes, including tissue growth regulation, cellular proliferation, development, and host defense [38], with significant contributions of hemocytes in mediating these functions [39,40]. Under both homeostatic or infected conditions, Eiger modulates Drosophila hemocyte function to promote survival through actions as a chemoattractant [41], inducer of cell death [42], or regulator of phagocytosis [43][44][45]. While recent studies have expanded our knowledge on how TNF signaling influences the function of immune cells in other insect species [46], the role of TNF signaling in the mosquito innate immune system remains unclear.…”

When the microbiome shapes the host: immune evolution implications for infectious disease

“…As such, mechanisms of defence like ROS bursts or phagocytosis may be specifically useful against Gram-positive bacteria because alternatives like AMPs are ineffective for one reason or another. While the picture is less clear for what defence(s) are effective against the microsporidian parasite Tubulinosema ratisbonensis , phagocytosis is also uniquely important for host survival upon systemic infection [ 31 ]. More generally, eukaryotic parasites tend to be combatted by cellular responses, most likely because any molecular responses that immune cells use are made more effective by concentrating their effects through trapping parasites in networks of immune cells [ 32 , 33 ].…”

When the microbiome shapes the host: immune evolution implications for infectious disease

“…As such, mechanisms of defence like ROS bursts or phagocytosis may be specifically useful against Grampositive bacteria because alternatives like AMPs are ineffective for one reason or another. While the picture is less clear for what defence(s) are effective against the microsporidian parasite Tubulinosema ratisbonensis, phagocytosis is also uniquely important for host survival upon systemic infection [28]. More generally, eukaryotic parasites tend to be combatted by cellular responses, most likely because any molecular responses that immune cells use are made more effective by concentrating their effects through trapping parasites in networks of immune cells [29,30].…”