Abstract
Activation of the insect innate immune system is dependent on a limited number of pattern recognition receptors (PRRs) capable of interacting with pathogen-associated molecular pattern. Here we report a novel role of an alternatively spliced hypervariable immunoglobulin domain-encoding gene, Dscam, in generating a broad range of PRRs implicated in immune defense in the malaria vector Anopheles gambiae. The mosquito Down syndrome cell adhesion molecule gene, AgDscam, has a complex genome organization with 101 exons that can produce over 31,000 potential alternative splice forms with different combinations of adhesive domains and interaction specificities. AgDscam responds to infection by producing pathogen challenge-specific splice form repertoires. Transient silencing of AgDscam compromises the mosquito's resistance to infections with bacteria and the malaria parasite Plasmodium. AgDscam is mediating phagocytosis of bacteria with which it can associate and defend against in a splice form–specific manner. AgDscam is a hypervariable PRR of the A. gambiae innate immune system.
Highlights
The insect’s innate immune system is activated upon specific recognition of pathogen-associated molecular patterns by germline-encoded pattern recognition receptors (PRRs)
The E. coli and S. aureus strains used in this study are most likely not natural pathogens to which A. gambiae mosquitoes are exposed to in the field, and A. gambiae may not have evolved a highly specific AgDscam splice form for these bacteria
The broad range of constitutively expressed AgDscam receptor molecules will narrow down to a more specific receptor repertoire that is more compatible with the infectious organism upon immune activation
Summary
The insect’s innate immune system is activated upon specific recognition of pathogen-associated molecular patterns by germline-encoded pattern recognition receptors (PRRs). Splice form–specific and direct interaction has been shown for recombinant D. melanogaster Dscam molecules to bacteria [18] The significance of this splice form pathogen–association specificity for immune defense was demonstrated by the differential resistance patterns of mosquitoes to the different pathogens upon selective silencing of specific AgDscam splice form repertoire mRNAs [53]. The E. coli and S. aureus strains used in this study are most likely not natural pathogens to which A. gambiae mosquitoes are exposed to in the field, and A. gambiae may not have evolved a highly specific AgDscam splice form for these bacteria Through this mechanism, the mosquito can more efficiently target specific pathogens by selective production of a limited range of PRRs with increased affinity and defense activity, instead of producing a very broad repertoire of random splice forms that would only contain a small proportion of pathogen-specific receptors
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