RESUMEN
Mosquitoes use effective immune responses, including phagocytosis, to fight microbial infection. Here we show that in an Anopheles gambiae immune responsive cell line, RGD recognizing receptors play an important role in the phagocytic response, suggesting overlap between molecular components implicated in adhesion and phagocytosis. Integrins are a major class of adhesive receptors that recognize ligands containing an RGD motif. We have cloned a gene encoding a new beta integrin, BINT2, and demonstrated its involvement in Escherichia coli engulfment. Based on molecular modeling, we propose a structural reason for the role of BINT2, but not BINT1, on phagocytosis of Gram-negative bacteria. Using bioinformatic tools, we have identified and compared the complete A. gambiae integrin repertoire as a prelude to a future systematic functional study.
Asunto(s)
Anopheles/metabolismo , Anopheles/microbiología , Escherichia coli/fisiología , Proteínas de Insectos/fisiología , Cadenas beta de Integrinas/fisiología , Fagocitosis/fisiología , Animales , Anopheles/citología , Adhesión Celular/fisiología , Línea Celular , Clonación Molecular , Cristalografía por Rayos X , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Cadenas beta de Integrinas/química , Cadenas beta de Integrinas/metabolismo , Modelos Moleculares , Filogenia , Receptores Inmunológicos/fisiología , Receptores de Péptidos/fisiología , Staphylococcus aureus/fisiologíaRESUMEN
We have used confocal microscopy and an antibody against Anopheles gambiae beta integrin to study this protein's distribution in the mosquito midgut and its relationship to invading Plasmodium berghei parasites. An extensive reorganization of integrin is seen to take place in the midgut epithelial cells following the uptake of either non-infected or parasite-infected blood meal, probably reflecting the reshaping of the gut due to the presence of the food bolus and the peritrophic membrane that surrounds it. Furthermore, malaria parasites are coated with beta integrin immediately upon entry into the epithelium, independent of whether they develop intra- or extracellularly. Although this coat is shed a few days after the invasion, beta integrin remains concentrated in the cells surrounding the maturing oocyst for several days. Finally, the antibody detects a structural change in the midgut epithelial cells in the immediate vicinity of the invading ookinete, which is consistent with Plasmodium-induced apoptosis followed by wound healing. This intimate association suggests a specific role of beta integrin in the invasion process.