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Péptido YY: un péptido antimicrobiano de células de Paneth que mantiene el comensalismo intestinal de Candida
Joseph F Pierre1,2, Brian M Peters3, Diana La Torre1
1Department of Medicine, University of Chicago, Chicago, IL, USA.
Science (New York, N.Y.)
|August 3, 2023
Resumen
El péptido YY (PYY1-36), producido por las células Paneth intestinales, funciona como un péptido antimicrobiano antifúngico (AMP). Se dirige selectivamente a las hifas de Candida albicans, alterando las membranas y promoviendo el equilibrio fúngico intestinal.
Área de la Ciencia:
- Microbiología
- Gastroenterología
- Inmunología
Sus antecedentes:
- Los péptidos intestinales de los mamíferos regulan el apetito, las secreciones, la motilidad y la microbiota.
- Las células Paneth (PC) en el epitelio intestinal secretan varios péptidos.
- El papel de las isoformas específicas del péptido YY (PYY) en la defensa intestinal no se comprende completamente.
Objetivo del estudio:
- Investigar las propiedades antimicrobianas del péptido YY (PYY1-36) producido por las células Paneth intestinales (PC).
- Determinar los objetivos y mecanismos específicos de la actividad antimicrobiana del PC-PYY.
- Para aclarar el papel de PC-PYY en el mantenimiento del comensalismo fúngico intestinal.
Principales métodos:
- Caracterización del PC-PYY como un péptido antimicrobiano (AMP).
- Evaluación de la actividad antibacteriana y antifúngica del PC-PYY.
- Análisis de la interacción de PC-PYY con las hifas fúngicas, incluida la ruptura de la membrana y los cambios en la transcripción.
- Evaluación del efecto de PC-PYY en la morfología de Candida albicans (hifas frente a levadura).
Principales resultados:
- El péptido YY (PYY1-36), pero no PYY3-36, es expresado por las células Paneth intestinales (PC) y funciona como un péptido antimicrobiano (AMP).
- PC-PYY muestra actividad antifúngica selectiva contra la virulenta Candida albicans hyphae, pero no contra la forma de levadura.
- PC-PYY, una molécula catiónica, interrumpe las superficies aniónicas de las hifas fúngicas, lo que lleva a daños en la membrana y a la reprogramación transcripcional.
- Esta reprogramación favorece el fenotipo de la levadura, contribuyendo al mantenimiento del comensalismo de hongos intestinales.
Conclusiones:
- Las células epiteliales de Paneth (PC) secretan el péptido YY (PYY1-36) como un péptido antimicrobiano antifúngico (AMP).
- PC-PYY ataca selectivamente y interrumpe las hifas de Candida albicans, contribuyendo a la regulación de las poblaciones de hongos intestinales.
- PC-PYY juega un papel en el mantenimiento del equilibrio de los comensales fúngicos dentro del intestino de los mamíferos.
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