RESUMEN
Innate immunity is the first line of host defense against invading pathogens, and it is recognized by a variety of pattern recognition molecules, including mannose-binding lectin (MBL). MBL binds to mannose and N-acetylglucosamine residues present on the glycopolymers of microorganisms. Human serum MBL functions as an opsonin and activates the lectin complement pathway. However, which glycopolymer of microorganism is recognized by MBL is still uncertain. Here, we show that wall teichoic acid of Staphylococcus aureus, a bacterial cell surface glycopolymer containing N-acetylglucosamine residue, is a functional ligand of MBL. Whereas serum MBL in adults did not bind to wall teichoic acid because of an inhibitory effect of anti-wall teichoic acid antibodies, MBL in infants who had not yet fully developed their adaptive immunity could bind to S. aureus wall teichoic acid and then induced complement C4 deposition. Our data explain the molecular reasons of why MBL-deficient infants are susceptible to S. aureus infection.
Asunto(s)
Lectina de Unión a Manosa de la Vía del Complemento , Lectina de Unión a Manosa/metabolismo , Manosa/metabolismo , Infecciones Estafilocócicas/metabolismo , Staphylococcus aureus/metabolismo , Ácidos Teicoicos/metabolismo , Adulto , Animales , Anticuerpos Antibacterianos/química , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/farmacología , Células CHO , Pared Celular/química , Pared Celular/inmunología , Pared Celular/metabolismo , Complemento C4/química , Complemento C4/inmunología , Complemento C4/metabolismo , Cricetinae , Cricetulus , Susceptibilidad a Enfermedades/inmunología , Susceptibilidad a Enfermedades/metabolismo , Humanos , Lactante , Manosa/química , Lectina de Unión a Manosa/química , Lectina de Unión a Manosa/deficiencia , Lectina de Unión a Manosa/inmunología , Infecciones Estafilocócicas/inmunología , Staphylococcus aureus/química , Staphylococcus aureus/inmunología , Ácidos Teicoicos/química , Ácidos Teicoicos/inmunologíaRESUMEN
Genetic studies have elegantly characterized the innate immune response in Drosophila melanogaster. However, these studies have a limited ability to reveal the biochemical mechanisms underlying the innate immune response. To investigate the biochemical basis of how insects recognize invading microbes and how these recognition signals activate the innate immune response, it is necessary to use insects, from which larger amounts of hemolymph can be extracted. Using the larvae from two species of beetle, Tenebrio molitor and Holotrichia diomphalia, we elucidated the mechanisms underlying pathogenic microbe recognition. In addition, we studied the mechanism of host defense molecule amplification. In particular, we identified several pattern recognition proteins, serine proteases, serpins and antimicrobial peptides and examined how these molecules affect innate immunity.