Anopheles appreciating the diversity of insect immunity

Sequencing the A. gambiae genome (Holt et al., 2002) in 2002 gave a great boost to research on disease vectors, and the availability of two insect genomes facilitated the introduction of new ideas, approaches, and recruits to the field of vector biology. Genome comparisons provided opportunities for comprehensive comparative studies of insect immunity and other physiological or developmental systems, with the A. gambiae genome being quickly adopted by the community of drosophilists for comparative bioinformatic and experimental studies. The acquisition of comparative information in both genomics and innate immunity created the new and dynamic field of immunogenomics.

Mosquitoes and fruit flies are both Diptera, but they have adopted very different life strategies.

Table 6.1 The established framework of insect innate immunity allows for the classification of genes and gene families into broad functional categories of recognition, modulation, signal transduction, and effector components as well as responses to oxidative stress and RNA. These categories consist of genes from pathways and protein families implicated in immune responses through experimental research, and together they form the basis of the currently recognized insect immune repertoire.

Table 6.1 The established framework of insect innate immunity allows for the classification of genes and gene families into broad functional categories of recognition, modulation, signal transduction, and effector components as well as responses to oxidative stress and RNA. These categories consist of genes from pathways and protein families implicated in immune responses through experimental research, and together they form the basis of the currently recognized insect immune repertoire.

Functional category

Abbreviation

Full name

Recognition

GNBPs (BGBPs)

Gram-negative-bacteria-binding proteins (1,3-p-D-glucan-binding proteins)

CTLs

C-type lectins (also important modulators)

FREPs (FBNs)

Fibrinogen-related proteins (fibrinogen-domain immunolectins)

GALEs

Galactoside-binding lectins

LRIMs

Leucine-rich-repeat immune proteins

MLs

MD2-like proteins (lipid recognition)

PGRPs

Peptidoglycan-recognition proteins

SCRs

Scavenger receptors (SRCR(A), CD36(B), and CCP-MAM(C) types)

TEPs

Thioester containing proteins

Modulation

CLIPs

Clip-domain serine proteases (also serine protease homologues)

IAPs

Inhibitors of apoptosis

SRPNs

Serpins, serine protease inhibitors

Signal transduction

PATHWAYS

Toll and Imd pathway genes

JAK/STATs

Janus kinases/signal transducers and activators of transcription

RELs

Rel-like NF-kB proteins (transcription factors)

SPZs

Spatzle-like proteins (cytokines)

Tolls

Toll-like receptors

Effectors

AMPs

Antimicrobial peptides

CASPs

Caspases

LYSs

Lysozymes

ProPOs

Prophenoloxidases (melanization)

Oxidative defence

CATs

Catalases

PRDXs

Peroxidases (glutathione (GPX), haem (HPX), and thioredoxin (TPX))

SODs

Superoxide dismutases (CuZn and MnFe types)

RNA defence

DCRs

Dicers

AGOs

Argonautes

Haematophagy (blood feeding) provides the rich meal of proteins and lipids required by the female mosquito to develop a batch of eggs. However, blood feeding exposes her to pathogens in the vertebrate blood. The first genome-scale comparison between immune repertoires of two invertebrates identified 242 mosquito genes from 18 families with putative immune functions, based on experimental work in mosquitoes, or comparisons with genes of known immune-related functions in fruit flies and other insects (Table 6.1) (Christophides et al., 2002). This study highlighted marked diversification between the two species, with prominent gene family expansions among immune recognition, modulation, and effector components.

Global comparative analysis of sequence identities in Anopheles-Drosophila orthologues highlighted enhanced divergence of proteins linked to defence and immunity through gene ontology (Zdobnov et al., 2002). Additionally, functional-domain comparisons identified major immunity gene family expansions or reductions in these two species (Zdobnov et al., 2002). Analysis of the immune repertoires against the backdrop of the entire proteomes revealed a clear deficit of orthologues, particularly in immune-related gene families implicated in recognition, signal modulation, and effector systems (Christophides et al., 2002, 2004). In marked contrast, the key immune signal transduction components showed striking orthology, in both the Toll and Imd pathways. These comparative studies laid down an initial conceptual framework of insect innate immunity that was further elaborated to accommodate major observed variations in sequence diversity, between distinct functional categories of immune gene families. Subsequent large-scale functional studies, including microarray analysis and reverse genetics via RNA interference (RNAi), revealed mechanisms underlying this framework. The Anopheles studies have suggested that mosquitoes are largely refractory to malaria parasites; this resistance is largely attributable to the mosquito's systemic and local epithelial immunity (Sinden et al, 2004; Vlachou and Kafatos, 2005). The highly variable vectorial capacities of different mosquito species and strains reflect a dynamic relationship between pathogens and vectors: a balance between pathogen evasion or its effective detection and elimination by the vector immune system (see Chapter 7 in this volume).

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment