chapter 1 - Bentham Science

More documents

Recommendations

Info

Immune Response of Insects and Crustaceans HPFP: Recent Advances in Insects and Other Arthropods Vol. 1 63 excellent model organism to decipher the basic principles of innate immune responses [5]. Following the discovery of AMPs, which are infection-dependent inducible effector molecules, the ability to monitor AMP expression was rapidly established [6]. Genetic screening of these AMP reporter systems has led to the identification of two key nuclear factors (NF-B), DIF (dorsal-related immunity factor) and Relish, which control two distinct innate immune signaling pathways, the Toll and immune deficiency (imd) pathways, respectively [7, 8]. The Toll pathway is activated by fungal and Gram-positive bacteria and the imd pathway is predominantly activated by Gram-negative bacteria, which are mechanistically conserved in the mammalian Toll-like-receptor/Interleukin-1 receptor and tumor necrosis factor (TNF) receptor signaling pathways, respectively [5]. Subsequent genetic and RNAi screens led to the functional characterization of PRRs and proteases involved in activating the Toll pathway or melanization. The Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, which were originally found to be involved in developmental processes, are also involved in the antiviral response, tissue damage recovery, and hemocyte proliferation and differentiation [9, 10]. A recent proteomic analysis also identified crucial factors involved in hemolymph coagulation [11]. The horseshoe crab, belonging to the class of Merostomata, is commonly found in East Asia and North America. It is called a living fossil and there are at least four known species (Limulus polyphemus, Tachypleus tridentatus, Tachypleus gigas, and Carcinoscorpius rotundicauda). The horseshoe crab is highly useful for biochemical analysis and several hundred milliliters of hemolymph can be obtained from one horseshoe crab without threatening its life, and the largest single population of hemocytes in the hemolymph, granular hemocytes (~99%), is extremely sensitive to bacterial endotoxin LPS [12]. In the 1990s, using T. tridentatus whose habitats are coastal areas of the Kyushu Islands in Japan, Professor Iwanaga’s group at Kyushu University successively identified novel hemolymph proteins and clarified the detailed molecular mechanisms of the hemolymph coagulation cascades [13-15]. In this review, we provide an overview of current advances in our understanding of invertebrate innate immunity, based on studies performed mainly in Drosophila and horseshoe crab. Further elucidation of the detailed molecular mechanisms on both cellular and humoral innate immune reactions will enhance our understanding of the complexities of mammalian innate immune reactions. RECOGNITION OF PATHOGENS AND DANGERS The ingenious predictions of Professor Charles Janeway (1943-2003) led to the pattern recognition theory (e.g., host cells can discriminate ‘non-infectious self’ from ‘infectious non-self’) and it is now established that PAMP-PRR interactions are key initial processes in activating innate immune responses [1-4]. As summarized in Fig. 1, the innate immune response comprises multiple steps. Although this picture represents a combined overview from Drosophila and horseshoe crab studies, the basic principles can be applied to almost all metazoans, including mammals. Once host cells sense either a pathogen (e.g., PAMPs) or danger signal (damage-associated molecular pattern; DAMP), two pillars of the innate immune system, cellular and humoral responses are initiated to activate numerous defense reactions such as phagocytosis, encapusulation, AMPs and effector gene expression, and clot and melanization formation (Fig. 1). Using appropriate combinations of these defense reactions, hosts can efficiently eliminate invading pathogens and maintain homeostasis. Among various types of PRRs, one of the hallmark signaling PRRs in Drosophila is the peptidoglycan recognition receptor (PGRP) family, which detects peptidoglycans (PGN), an essential cell wall component in nearly all bacteria [16, 17]. The name PGRP was first introduced by Professor Ashida’s group [18] who purified a 19-kDa protein from silkworm (Bombyx mori) hemolymph based on its high binding affinity to bacterial PGNs and demonstrated its involvement in activating prophenoloxidase (proPO) cascades [18]. Subsequent cDNA cloning studies revealed that this PGRP family is evolutionarily conserved from insects to mammals. Several recently completed genome projects have also demonstrated at least 13 PGRPs with 19 spliced variants in D. melanogaster, 7 PGRPs with 9 spliced protein variants in Anopheles gambiae, and 4 PGRPs in both humans and mice [19-21]. All PGRPs have a conserved PGRP-domain (~165 amino acid
64 HPFP: Recent Advances in Insects and Other Arthropods Vol. 1 Goto and Kurata residues) at the C-terminal that has sequence similarity to N-acetyl-muramyl-alanine amidases, such as bacteriophage lysozymes. This homology also implies that PGRPs and prokaryotic N-acetyl-muramylalanine amidases evolved from a common ancestor gene [19-20]. Epithelial immune responses JAK/STAT ? ? ? DAMPs Imd Danger signals AMPs and effector genes expression Stress Host recognition ? Humoral immune responses Serine proteases cascades spz/Toll Serpins ? ? Coagulation proPO cascades activation ? ? Pathogens PAMPs (LPS, β-glucan, PGN etc..) Clot Melanization PRRs (PGRPs,GNBPs, lectins etc..) Cellular immune responses Figure 1: Schematic representation of combined Drosophila and horseshoe crab innate immune responses. Pathogens and danger signals are recognized by host cells through pattern recognition receptors (PRRs) and uncharacterized receptors, respectively. This host recognition triggers two major humoral and cellular immune responses. The humoral immune responses include activation of the innate immune signaling pathways and of proteolytic cascades, leading to coagulation and melanization. On the other hand, representative cellular immune responses include phagocytosis and encapusulation. Solid or dashed lines indicate clear or still unclear observations, respectively. Among the 13 known Drosophila PGRPs, there are 7 short transcripts (designated as PGRP-S; ~200 amino acids long) and 6 long transcripts (designated as PGRP-L; from 200 to 600 amino acids long). In general, short PGRPs are secreted and induced in response to bacterial infection, whereas long PGRPs are constitutively expressed on the cell surface or integrated into plasma membranes [22]. Extensive Drosophila genetic screens combined with sophisticated molecular biological techniques, RNAi strategies and biochemical approaches have identified the individual molecular functions of each PGRP (Fig. 2) [17]. Briefly, PGRP-SA [23] and PGRP-SD [24] are involved in activating the Toll pathway in response to Gram-positive bacterial infection. PGRP-LC is involved in activating the imd pathway in response to Gram-negative bacterial infection [25]. PGRP-LE uniquely has two acidic domains and is involved in activating the imd pathway and the proPO cascade [26, 27]. PGRP-LE can also function as an intracellular receptor [28], and is involved in the defense against infection by the intracellular bacteria Listeria monocytogenes via autophagy mechanisms that are totally independent of the Toll and imd pathways [29- 30]. In contrast to these pattern recognition receptors (PGRP-SA, -SD, -LC and -LE), six other PGRPs (PGRP-SB1, -SB2, -SC1a, -SC1b, -SC2, and -LB) are proposed to possess amidase activity and to be involved in peptidoglycan degradation [31, 32]. Three independent groups demonstrated catalytic roles of PGRP-SC1/SC2 [33], PGRP-LB [34], and PGRP-SB1 [35] for the modulation of the imd pathway, functioning as scavengers. Versatile functions of PGRPs are also reported (Fig. 2). ? Encapsulation ? Phagocytosis
Page 2 and 3: Hemolymph Proteins and Functional P
Page 4 and 5: CONTENTS Foreword i Preface ii List
Page 6 and 7: ii PREFACE The aim of this eBook
Page 8 and 9: iv Giancarlo Lopez-Martinez Departm
Page 12 and 13: Hemolymph Lipoproteins: Role in Ins
Page 14 and 15: Adipokinetic Hormones and Their Rol
Page 16 and 17: 32 Hemolymph Proteins and Functiona
Page 18 and 19: 34 HPFP: Recent Advances in Insects
Page 22 and 23: 78 Hemolymph Proteins and Functiona
Page 24 and 25: 80 HPFP: Recent Advances in Insects
Page 26 and 27: Structures and Functions of Insect
Page 30 and 31: Neurohormones and Second Messengers
Page 32 and 33: Role of Conventional and Unconventi
Page 36 and 37: Insulin-Related Peptides in Insects
Page 38 and 39: ENF Peptides HPFP: Recent Advances

chapter 1 - Bentham Science

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?