Recent Advances in <i>Drosophila</i> Cellular and Humoral Innate Immunity

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Background

The fruit fly Drosophila melanogaster is an established tool to study mechanisms of innate immunity. Drosophila flies and larvae launch elegant humoral and cellular innate immune responses against bacteria, viruses, fungi and parasites. The humoral immune response is based on microbial recognition primarily by peptidoglycan recognition proteins leading to the production of antimicrobial peptides (AMPs). In the past few decades, Drosophilists have dissected how flies react to systemic bacterial and fungal infections at the molecular level and shown how these mechanisms are conserved from human to man. Fly humoral immune response is mainly mediated by two evolutionarily conserved NF-κB signaling pathways, the Toll and the Immune deficiency (Imd) pathways. The discovery of the Toll receptor as a key regulator of immune response, first in cultured Drosophila cells and then in Drosophila in vivo, formed the basis of the Toll-Like Receptor (TLR) research in humans and mammals. More recently, this field has broadened considerably, including e.g. the antimicrobial responses taking place in the gut. Another interesting aspect related to innate immunity is the antiviral immune mechanisms found in Drosophila. Best understood are the mechanisms based on RNAi, primarily against RNA virus infections. More recently, the evolutionarily conserved molecule STING has been shown to integrate responses against both viruses and bacteria.

Drosophila blood cells, hemocytes, have multiple roles in the cellular arm of the innate immune response, such as recognition, phagocytosis, encapsulation and the killing of pathogens. Compared to the humoral immune responses, the molecular underpinnings of the cellular immunity are still not well understood. Hemocytes are traditionally classified into three main groups: the phagocytic plasmatocytes, crystal cells and lamellocytes, which are specialized in encapsulating parasites. The first wave of hematopoiesis occurs in embryonic head mesoderm, giving rise to plasmatocytes. In larvae, hemocyte differentiation occurs in the lymph glands, where it has been described in considerable detail. Similar events take place in the peripheral populations of hemocytes, although the molecular mechanisms are still unclear. The on-going work to develop new hemocyte markers will lead to more precise understanding of hematopoiesis and hemocyte populations and their relationships, which in turn results in new discoveries in the cellular innate immunity.

This Research Topic aims to provide recent advances in Drosophila innate immunity, with a focus on research opening new ways for using Drosophila as a model for different features of immunity. We welcome the submission of Original Research, Review, Mini-Review, Methods and Perspective articles covering, but not limited to, the following sub-topics:

1. Drosophila as a promising model system to unravel complex tissue interactions during an immune challenge, e.g. between sensory neurons, muscles, fat body, epithelia, gut, and hemocytes.
2. Signaling networks, including but not limited to NF-κB signaling, controlling the organismal response, from pathogen recognition to mounting an immune response.
3. Antimicrobial responses taking place in the gut, where the interaction with the endogenous microbiota plays an important role.
4. Metabolic changes in the activation of the immune responses.
5. The role of non-coding RNA molecules in regulating and fine-tuning Drosophila immune responses.
6. Drosophila as a model to study the immune mechanisms against viral infections.

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Keywords: Drosophila, innate immunity, signaling, hemocytes, antimicrobial peptides

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