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Drosophila as a model system to unravel the layers of innate immunity to infection.

Kounatidis I, Ligoxygakis P - Open Biol (2012)

Bottom Line: Innate immunity relies entirely upon germ-line encoded receptors, signalling components and effector molecules for the recognition and elimination of invading pathogens.The fruit fly Drosophila melanogaster with its powerful collection of genetic and genomic tools has been the model of choice to develop ideas about innate immunity and host-pathogen interactions.Here, we review current research in the field, encompassing all layers of defence from the role of the microbiota to systemic immune activation, and attempt to speculate on future directions and open questions.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genes and Development, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.

ABSTRACT
Innate immunity relies entirely upon germ-line encoded receptors, signalling components and effector molecules for the recognition and elimination of invading pathogens. The fruit fly Drosophila melanogaster with its powerful collection of genetic and genomic tools has been the model of choice to develop ideas about innate immunity and host-pathogen interactions. Here, we review current research in the field, encompassing all layers of defence from the role of the microbiota to systemic immune activation, and attempt to speculate on future directions and open questions.

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Layers of Drosophila immunity: (a) receptors found on the surface of Drosophila macrophages, (b) schematic of the melanization reaction and (c) coagulation. The link to pathogen recognition in both (b) and (c) still remains elusive. PPAE, pro-phenoloxidase activating enzyme.
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RSOB120075F1: Layers of Drosophila immunity: (a) receptors found on the surface of Drosophila macrophages, (b) schematic of the melanization reaction and (c) coagulation. The link to pathogen recognition in both (b) and (c) still remains elusive. PPAE, pro-phenoloxidase activating enzyme.

Mentions: One of the most powerful and immediate ways for fruit flies to eliminate apoptotic bodies, bacterial infection or fungal spores in the haemolymph is by their removal through receptor-mediated recognition and phagocytosis. Drosophila phagocytes have been used as a model for ‘professional’ mammalian phagocytosis (for review see [60]). This is because, during development, dead cells are recognized by evolutionary-conserved receptors such as Croquemort (CRO, the CD36 paralogue) [61] and Draper (the LPS recognition protein (RP) paralogue) [62], although the latter also recognizes lipoteichoic acid from Staphylococcus aureus and mediates uptake of this bacterium [63]. Studies of Drosophila S2 cells, which share many features with mammalian macrophages and are amenable to RNAi, identified phagocytic receptors relevant to host immunity, such as members of the scavenger receptor family Peste and dSR-C1 [64,65], peptidoglycan PGRP-LC [66], members of the Nimrod family of proteins Eater [67] and Nimrod C1 [68] and the IgSF-domain protein Dscam [69]. A summary of these receptors is schematically presented in figure 1a. However, the question of which components of the bacterial cell wall are recognized, and how, by these receptors is still open (for PGRP-LC see below). Nonetheless, significant advances have been made in the elucidation of intracellular signalling and actin regulation [70]. Measurements of time needed to eliminate pathogens by phagocytosis have resulted in describing an impressive capacity: systemically infected larvae with 3000 bacteria can eliminate almost 95 per cent of them in 30 min [53]. It is some hours later that AMP gene expression peaks and therefore a pertinent question was why larvae need AMPs at all. An interesting proposition came not from Drosophila but from Tenebrio molitor where the same time-course was observed in adults [71]. Rolf and co-workers proposed that the timing was crucial in order for AMPs to ‘meet’ a dramatically reduced number of bacteria and thus diminish the possibility for induction of resistance [71]. Moreover, their sustained expression and presence in the haemolymph long after the infection was cleared provided protective immunity.Figure 1.


Drosophila as a model system to unravel the layers of innate immunity to infection.

Kounatidis I, Ligoxygakis P - Open Biol (2012)

Layers of Drosophila immunity: (a) receptors found on the surface of Drosophila macrophages, (b) schematic of the melanization reaction and (c) coagulation. The link to pathogen recognition in both (b) and (c) still remains elusive. PPAE, pro-phenoloxidase activating enzyme.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376734&req=5

RSOB120075F1: Layers of Drosophila immunity: (a) receptors found on the surface of Drosophila macrophages, (b) schematic of the melanization reaction and (c) coagulation. The link to pathogen recognition in both (b) and (c) still remains elusive. PPAE, pro-phenoloxidase activating enzyme.
Mentions: One of the most powerful and immediate ways for fruit flies to eliminate apoptotic bodies, bacterial infection or fungal spores in the haemolymph is by their removal through receptor-mediated recognition and phagocytosis. Drosophila phagocytes have been used as a model for ‘professional’ mammalian phagocytosis (for review see [60]). This is because, during development, dead cells are recognized by evolutionary-conserved receptors such as Croquemort (CRO, the CD36 paralogue) [61] and Draper (the LPS recognition protein (RP) paralogue) [62], although the latter also recognizes lipoteichoic acid from Staphylococcus aureus and mediates uptake of this bacterium [63]. Studies of Drosophila S2 cells, which share many features with mammalian macrophages and are amenable to RNAi, identified phagocytic receptors relevant to host immunity, such as members of the scavenger receptor family Peste and dSR-C1 [64,65], peptidoglycan PGRP-LC [66], members of the Nimrod family of proteins Eater [67] and Nimrod C1 [68] and the IgSF-domain protein Dscam [69]. A summary of these receptors is schematically presented in figure 1a. However, the question of which components of the bacterial cell wall are recognized, and how, by these receptors is still open (for PGRP-LC see below). Nonetheless, significant advances have been made in the elucidation of intracellular signalling and actin regulation [70]. Measurements of time needed to eliminate pathogens by phagocytosis have resulted in describing an impressive capacity: systemically infected larvae with 3000 bacteria can eliminate almost 95 per cent of them in 30 min [53]. It is some hours later that AMP gene expression peaks and therefore a pertinent question was why larvae need AMPs at all. An interesting proposition came not from Drosophila but from Tenebrio molitor where the same time-course was observed in adults [71]. Rolf and co-workers proposed that the timing was crucial in order for AMPs to ‘meet’ a dramatically reduced number of bacteria and thus diminish the possibility for induction of resistance [71]. Moreover, their sustained expression and presence in the haemolymph long after the infection was cleared provided protective immunity.Figure 1.

Bottom Line: Innate immunity relies entirely upon germ-line encoded receptors, signalling components and effector molecules for the recognition and elimination of invading pathogens.The fruit fly Drosophila melanogaster with its powerful collection of genetic and genomic tools has been the model of choice to develop ideas about innate immunity and host-pathogen interactions.Here, we review current research in the field, encompassing all layers of defence from the role of the microbiota to systemic immune activation, and attempt to speculate on future directions and open questions.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genes and Development, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.

ABSTRACT
Innate immunity relies entirely upon germ-line encoded receptors, signalling components and effector molecules for the recognition and elimination of invading pathogens. The fruit fly Drosophila melanogaster with its powerful collection of genetic and genomic tools has been the model of choice to develop ideas about innate immunity and host-pathogen interactions. Here, we review current research in the field, encompassing all layers of defence from the role of the microbiota to systemic immune activation, and attempt to speculate on future directions and open questions.

Show MeSH