A Protean Insect Receptor Holds the Key to Broad-Based Pathogen Recognition

1101 Anything that’s alive runs the risk of infection. How you respond to infection, however, depends on where you sit on the evolutionary tree. Humans and other vertebrates can fend off billions of pathogens by routinely recombining bits of genes for surface molecules on the cells charged with pathogen recognition. Insects and other invertebrates rely to a large degree on the pathogen recognition molecules (called pattern recognition receptors) they were born with. When a pattern recognition receptor detects a pathogen—based on what’s known as its pathogen-associated molecular pattern—the receptor can launch a direct attack that either engulfs the invader, through encapsulation or phagocytosis, or triggers signaling pathways that regulate immune system genes involved in killing the pathogen. In a new study, Yuemei Dong, Harry Taylor, and George Dimopoulos found a mosquito gene that vastly boosts the ability of insect pattern recognition receptors to detect pathogens. Originally implicated in neuron development, the gene can create a plethora of receptors for the malaria vector Anopheles gambiae. The AgDscam gene—short for Anopheles gambiae Down syndrome cell adhesion molecule gene—has 101 proteincoding regions (called exons) that can be mixed and matched after transcription to produce over 31,000 possible alternative splice forms with different properties. Thus, while B cell and T cell receptor diversity is generated largely at the gene sequence level before transcription, AgDscam diversity is produced by reshuffl ing sections of gene transcripts before translation into protein. A Protean Insect Receptor Holds the Key to Broad-Based Pathogen Recognition