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Las células NK deciduales transfieren granulisina para matar selectivamente las bacterias en los trofoblastos

Ângela C Crespo¹, Sachin Mulik², Farokh Dotiwala²

¹Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; PhD Programme in Experimental Biology and Biomedicine, Center for Neurosciences and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.

|August 22, 2020

Resumen

Las células inmunes maternas transfieren el péptido antimicrobiano granulisina (GNLY) a través de nanotubos para proteger a la placenta de la infección. Este mecanismo mata a los patógenos sin dañar la interfaz madre-fetal, asegurando el éxito del embarazo.

Área de la Ciencia:

Inmunología
Biología de la reproducción
Microbiología

Sus antecedentes:

Las células NK (dNK) maternas son cruciales para el éxito de la placentación.
Los mecanismos precisos por los que las células dNK protegen a la placenta de la infección mientras mantienen la tolerancia fetal siguen siendo incompletamente entendidos.

Objetivo del estudio:

Para investigar el papel de las células dNK en la defensa placentaria contra la infección.
Esclarecer el mecanismo de acción antimicrobiana de las células dNK, centrándose en la transferencia de granulisina (GNLY).

Principales métodos:

Análisis de la expresión de GNLY en las células dNK humanas.
Investigación de la transferencia de GNLY a través de nanotubos a los trofoblastos.
Evaluación de la eficacia de GNLY contra Listeria monocytogenes (Lm) en cultivos placentarios humanos, líneas celulares de trofoblastos y un modelo de ratón.
Comparación de los resultados del embarazo en ratones GNLY transgénicos y de tipo salvaje infectados con Lm.

Principales resultados:

Las células dNK humanas expresan altos niveles de GNLY y lo transfieren a los trofoblastos extravilosos a través de nanotubos.
El GNLY transferido mata eficazmente el Lm intracelular en los trofoblastos sin causar la muerte celular de los trofoblastos.
La transferencia de GNLY reduce significativamente las cargas de Lm en los tejidos placentarios y fetales, mejorando el éxito del embarazo en ratones transgénicos de GNLY.
Las células NK periféricas (pNK) también utilizan la transferencia de GNLY para eliminar bacterias en otras células inmunes.

Conclusiones:

La transferencia de granulisina a través de nanotubos es un mecanismo clave mediante el cual las células dNK maternas protegen a la placenta de la infección bacteriana.
Esta estrategia de defensa mediada por GNLY preserva la integridad de la barrera materno-fetal, asegurando un embarazo exitoso.
Los hallazgos revelan una nueva vía para la defensa inmune en la interfaz madre- feto y en otros contextos inmunológicos.

Palabras clave:

Listeria monocytogenes y sus derivados Granulado citotóxico Células NK decidales Trófoblasto extravilloso Granulisina y sus derivados Tolerancia entre la madre y el feto Los nanotubos embarazo

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