Intestinal lipid droplets as novel mediators of host-pathogen interaction inDrosophila

Abstract

Lipid droplets (LDs) are lipid-carrying multifunctional organelles, which might also interact with pathogens and influence the host immune response. However, the exact nature of these interactions remains currently unexplored. Here we show that systemic infection of Drosophila adult flies with non-pathogenic Escherichia coli , the extracellular bacterial pathogen Photorhabdus luminescens or the facultative intracellular pathogen Photorhabdus asymbiotica results in intestinal steatosis marked by lipid accumulation in the midgut. Accumulation of LDs in the midgut also correlates with increased whole-body lipid levels characterized by increased expression of genes regulating lipogenesis. The lipid-enriched midgut further displays reduced expression of the enteroendocrine-secreted hormone, Tachykinin. The observed lipid accumulation requires the Gram-negative cell wall pattern recognition molecule, PGRP-LC, but not PGRP-LE, for the humoral immune response. Altogether, our findings indicate that Drosophila LDs are inducible organelles, which can serve as markers for inflammation and, depending on the nature of the challenge, they can dictate the outcome of the infection.

TOR signalling is required for host lipid metabolic remodelling and survival following enteric infection inDrosophila

“…A central theme of our work is that alterations in host lipid metabolism are important component of immune responses. This is supported by previous studies in flies that have described how both intestinal and fat body lipid metabolism are needed for effective immune responses (Chakrabarti et al, 2014; Harsh et al, 2019; Kamareddine et al, 2018; Lee et al, 2018; Martinez et al, 2020). We pinpoint TOR as a central modulator of enteric infection-mediated changes in lipid metabolism, likely as a mechanism of infection tolerance.…”

Physiological and Pathological Regulation of Peripheral Metabolism by Gut-Peptide Hormones in Drosophila

“…Note that, PGRP-LC/Rel signaling, which is shown to regulate Tk production, could be modulated by various PGNs derived by non-commensal bacteria as well (Royet and Charroux, 2013). Another group recently showed that septic, but not oral, infection of bacterial pathogen Photorhabdus luminescens, Photorhabdus asymbiotica, or non-pathogenic Escherichia coli modulate gut Tk production without affecting gut microbiota homeostasis, resulting in lipid accumulation in the gut and whole body (Harsh et al, 2019). This evidence indicates that gut-peptide hormone could be regulated by the circulating PGNs derived from non-commensal bacteria.…”

The Drosophila midgut and the systemic coordination of lipid-dependent energy homeostasis

“…As the primary barrier to external pathogens, the insect gastrointestinal tract has distinct cell types that promote both nutrient-sensing and bacterial-sensing [36], allowing for bidirectional communication between signaling pathways that respond to a variety of external cues (such as bacteria or dietary macronutrients). To this end, innate immune signaling pathways can locally (and subsequently throughout the organism) direct midgut lipid metabolism in response to diverse microbes and/or pathogens, often utilizing midgut-or microbe-derived signals that coordinate lipid-metabolic responses [31, [37][38][39][40]. This discrete control of lipid metabolism (and often TAG catabolism) helps shape energy homeostasis and limit pathogenesis in response to enteropathogenic infections that require both a complex balance of energy usage and maintenance, as well as a complex integration of a multitude of signaling networks.…”