Lectins in Insect Immunity

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DESCRIPTION: (provided by the applicant): Non-self recognition is an essential component of the insect defense system to fight infection. Recognition of non-self in insects is mainly accomplished by a set of pattern recognition receptors, which are proteins that bind to polysaccharides in the surface of pathogens or parasites. Such recognition initiates a variety of immune responses, including prophenoloxidase (PPO) activation and encapsulation. PPO activation involves a serine proteinase cascade, leading tc melanotic encapsulation of metazoan and protozoan parasites. In insect vectors of human diseases, detection and killing of parasites are not highly effective, perhaps because certain recognition receptors are lacking or do not interact with othei molecules to stimulate an adequate protective response. Little is known about the recognition process mediated by any pattern recognition receptors in insects, or the mechanisms by which a variety of immune responses are initiated by the recognition process. Lectins are primary candidates as pattern recognition receptors because they can bind to terminal sugars of glycoproteins and glycolipids on the surface of many pathogens. Four novel C-type lectins, immulectins (IMLs), have been isolated from the tobacco hornworm, Manduca sexta. IMLs are involved in PPO activation and encapsulation. Also, two IML-2-associated serine proteinase homologs (SPHs) identified in M. sexta are necessary for PPO activation by prophenoloxidase-activating proteinase (PAP). This proposal aims to test a general hypothesis that binding of IML-2 to the surface of a pathogen or parasite functions to localize phenoloxidase (P0) activation to the area surrounding the invading organism. A part of this hypothesis is that IML-2 bound to a parasite surface participates in assembly of a complex of plasma proteins that results in activation of PPO specifically at the surface of the invader. The specific aims are: 1. Investigate binding specificity of IML-2. The binding of IML-2 to carbohydrates on the surface of pathogens or parasites triggers immune responses. Further research is needed to determine the carbohydrate binding specificity of IML-2. 2. Study IML-2-SPH initiated assembly of a protein complex at a surface during PPC activation. Formation of hemolymph protein complexes on the surface of parasites may localize PPO activation on the site of invasion or on the surface of invading parasites. Experiments will be designed to investigate protein-proteil interactions among IML-2, SPH, PPO, and PAP.