Biology subjects

Dudzic, J. P.

Publications and source records attributed to Dudzic, J. P..

3 recordsLinked to original sources

bioRxiv2020

Comparative RNA-Seq Analyses of Drosophila Plasmatocytes Reveal Gene Specific Signatures In Response To Clean Injury And Septic Injury

Drosophila melanogasters blood cells (hemocytes) play essential roles in wound healing and are involved in clearing microbial infections. Here, we report the transcriptional changes of larval plasmatocytes after clean injury or infection with the Gram-negative bacterium Escherichia coli or the Gram-positive bacterium Staphylococcus aureus compared to hemocytes recovered from unchallenged larvae via RNA-Sequencing. This study reveals 676 differentially expressed genes (DEGs) in hemocytes from clean injury samples compared to unchallenged samples, and 235 and 184 DEGs in E. coli and S. aureus samples respectively compared to clean injury samples. The clean injury samples showed enriched DEGs for immunity, clotting, cytoskeleton, cell migration, hemocyte differentiation, and indicated a metabolic reprogramming to aerobic glycolysis, a well-defined metabolic adaptation observed in mammalian macrophages. Microbial infections trigger significant transcription of immune genes, with significant differences between the E. coli and S. aureus samples suggesting that hemocytes have the ability to engage various programs upon infection. Collectively, our data bring new insights on Drosophila hemocyte function and open the route to post-genomic functional analysis of the cellular immune response.

immunology↗

bioRxiv2019

Metabolic adjustment of Drosophila hemocyte number and sessility by an adipokine

In animals, growth is regulated by the complex interplay between paracrine and endocrine signals. When food is scarce, tissues compete for nutrients, leading to critical resource allocation and prioritization. Little is known about how the immune system maturation is coordinated with the growth of other tissues. Here, we describe a signaling mechanism that regulates the number of hemocytes (blood cells) according to the nutritional state of the Drosophila larva. Specifically, we found that the adipokine NimB5 is produced in the fat body upon nutrient scarcity downstream of metabolic sensors. NimB5 is then secreted and bind to hemocytes to down-regulate their proliferation and adhesion. Blocking this signaling loop results in conditional lethality when larvae are raised on a poor diet, due to excessive hemocyte numbers and insufficient energy storage. Similar regulatory mechanisms shaping the immune system in response to nutrient availability are likely to be widespread in animals.\n\nAuthor summaryDrosophila larval hemocytes (blood cells) are found in two compartments: the lymph gland considered as a reservoir, and the peripheral compartment. Peripheral hemocytes form sessile patches attached to the internal surface of the larval body wall or are found freely circulating in the hemolymph. Little is known about the signals that regulate hemocytes proliferation and localization in the peripheral compartment. In this study, we have identified a new gene, NimrodB5, coding for the NimB5 protein, which is secreted by the fat body and binds to hemocytes. NimB5 inhibits hemocyte proliferation while promoting sessility, leading to an increased number of circulating hemocytes and adhesion defects in NimB5 mutant. We show that nimrodB5 expression by the fat body is controlled by metabolic cues to adjust hemocyte number to the physiological state of the larvae.\n\nInterestingly, deregulation of NimB5 causes lethality when larvae are raised on a poor diet due to a defect in regulating hemocytes proliferation. In conclusion, we have identified a new adipokine that optimizes hemocytes number to the physiological state of larvae. Our study also reveals a major role of the fat body in peripheral hematopoiesis regulation and outline how it can be costly to maintain a basal immune defense.

immunology↗

bioRxiv2018

More than black and white: complex relationships involving serine proteases regulate the Toll pathway and the melanization response in Drosophila

The melanization response is a rapid and important defense mechanism in arthropods. Melanin is produced around wound sites and invading microorganisms by phenoloxidases (POs), which need to be activated by the sequential activation of an extracellular serine protease (SP) cascade. Drosophila melanogaster has been a useful genetic model for dissecting insect immune signaling, but understanding these proteolytic cascades has been complicated by the large number of SP genes, possibly with redundant function. Taking advantage of recently-generated null and compound mutants, we re-investigated the role of SPs involved in the melanization response in D. melanogaster and discovered phenotypes previously concealed in single mutant analysis. We found that two of them, Hayan and Sp7, can activate the melanization response in two different manners: Hayan is required in the local blackening of wound sites, while Sp7 regulates an alternate melanization reaction responsible for the clearance of septic infections with Staphylococcus aureus. We present evidence that both Sp7 and Hayan regulate the Toll NF-kB pathway. Sp7 is regulated by canonical Toll signaling downstream of PGRP-SA, ModSP, and Grass, leading to control of septic infections via a Sp7-dependent melanization response. Additionally, we found that Hayan and the Toll-regulating SP Psh are the result of a recent gene duplication. Using genetic manipulations, we reveal the hidden role for Hayan, alongside Psh, in propagating Toll signaling downstream of pattern recognition receptors. Thus, we describe the existence of two pathways leading to the melanization response and reveal previously unknown dynamics in the activation of the Toll pathway.

immunology↗