Insects exhibit robust resistance to infection. Historically, this led to their use in understanding the biochemical and cellular mechanisms underlying host resistance to microbial infection. While these early studies aided in the understanding of many aspects of the innate immune response (Boman, 1995), the question of the genetic and molecular basis of these mechanisms persisted. As a tractable genetic model, Drosophila melanogaster has emerged as a paradigm for deciphering the innate immune response of insects (Ferrandon et al., 2007; Lemaitre and Hoffmann, 2007). Overall, studies in the fruit fly have led to increased understanding of mechanisms of pathogen recognition, the molecular basis of immune signalling, and a description of the specific responses of insects to microbial infection.
In this chapter we discuss the mechanisms whereby Drosophila recognize foreign microbes, the signalling systems that regulate adapted responses against them, and the effector mechanisms used to control them. We will first focus our attention on the so-called systemic antimicrobial response. This response consists of the massive production of peptides or polypeptides, especially antimicrobial peptides (AMPs), by the fat body in response to the intrusion of bacteria or fungi into the haemolymph (Ferrandon et al., 2007; Lemaitre and Hoffmann, 2007). To some extent this defence mechanism shares similarities with the acute-phase response of mammals that leads to the production of acute-phase proteins by the liver, an equivalent of the insect fat body. Both responses involve the upregulation of immune genes by nuclear factor kB (NF-kB) and Janus kinase/signal transduction and activators of transcription (JAK/STAT) pathways. However, there are major differences: while the acute-phase response is induced by inflammatory cytokines produced by other cells, most of the systemic response of insects is activated by pattern-recognition receptors (PRRs) that directly sense microbial elicitors. In addition, the systemic response involves the production of many antimicrobial peptides that directly target microbial invaders, while acute-phase proteins aid in the clearance of microbes by other immune defence mechanisms, such as phagocytosis and complement. This specific feature of the insect systemic response is attributed to the open circulatory system of insects, and the relatively small volume of their haemocoel that allows antimicrobial peptides to accumulate and reach active concentrations. Recently, genomic profiling studies revealed that many factors are secreted by the fat body in addition to antimicrobial peptides, suggesting that the systemic immune response impacts almost all immune reactions occurring in the haemolymph, including clotting, melanization, and phagocytosis.
In most organisms, AMPs do not act systemic-ally, but are produced locally in specific tissues that are in contact with the external environment. This is the case for mammalian mucosa, such as the genital, respiratory, and digestive tracts. This local response also exists in insects such as Drosophila and mainly consists of the expression, either constitutive or inducible, of a subset of AMPs in epithelia. The second section of this chapter will focus on the local immune response, particularly gut epithelial immunity. Though less characterized than the systemic response, more and more evidence points to the critical role of the local immune response during natural infection by Drosophila pathogens.
Despite this compartmentalization of the immune response, there is not complete separation between the local and systemic response. Several recent studies suggest communication between the two systems. In the final section of this chapter, we will discuss current research themes exploring the integration of local and systemic immunity, as well as their integration in host physiology.
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