Chapter 2 : Responses to Microbial Infection: an Overview

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The studies on antimicrobial peptide identification were rapidly extended to other insect species and eventually to . During the past decade, the ease of genetic analysis has made the fruit fly an organism of choice for the study of innate host defense. This chapter concentrates on recent developments in this field of study. , like all insects, is very resistant to microbial infections, mounting a multifaceted reaction against invading non-self. Drosophila blood cells (hemocytes) play a significant role in host defense. Three mature hemocyte types are found in circulation: plasmatocytes, crystal cells, and lamellocytes. Infection-dependent melanization is the most immediate response following microbial challenge or septic injury and requires the activation of phenoloxidase (PO), which is an oxidoreductase that catalyzes the conversion of phenols to quinones. The chapter then focuses on humoral immunity. In the early 1990s it was shown that the promoters of the antimicrobial peptides (AMP) genes contained sequence motifs related to mammalian NF- κB response elements. The Imd pathway governs defenses against gram-negative bacteria by controlling the induction of a number of genes, including most of those encoding the antibacterial peptides. Genetic screens and an RNAi-based screen in macrophagelike cultured cells have recently identified PRRs in

Citation: Hoffmann J, Ligoxygakis P. 2004. Responses to Microbial Infection: an Overview, p 31-44. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch2

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The hallmark of the humoral response is the synthesis and secretion into the hemolymph of several potent AMPs by fat body cells. Seven of these families of small cationic peptides have been biochemically and molecularly characterized and are presented here. The gene copy numbers are shown in parentheses followed by the maximum concentration that each peptide can reach after infection. Their main biological activities in physiological concentrations are anti-gram-negative for Diptericins, Attacins, Cecropins, and Drosocin; anti-grampositive for Defensins; and antifungal for Drosomycins and Metchnikowin.

Citation: Hoffmann J, Ligoxygakis P. 2004. Responses to Microbial Infection: an Overview, p 31-44. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch2
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Present view of Toll-dependent induction of immune genes following fungal or gram-positive bacterial infection. One of the sensors of gram-positive infection is a circulating recognition protein, PGRP-SA. The recognition receptor(s) for fungi is not yet known. Conversely, it is not clear how PGRP-SA signals to Spz and whether plays a role in inhibiting activation of the proteolytic cascade triggered by gram-positive bacteria as in the one for fungi. Finally, the signaling pathways and the ligands of other Tolls remain to be identified.

Citation: Hoffmann J, Ligoxygakis P. 2004. Responses to Microbial Infection: an Overview, p 31-44. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch2
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The Imd pathway controls the defense against gram-negative bacteria. It is relevant here to note that the receptor is still unknown. The putative transmembrane PGRP-LC does not qualify as one but rather is more of a part of an extensive receptor–adaptor complex (see also text).

Citation: Hoffmann J, Ligoxygakis P. 2004. Responses to Microbial Infection: an Overview, p 31-44. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch2
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