Shaping Healthy Immune Early Life Dynamics: role of the virome in undernutrition

Descripción del proyecto

El desarrollo inmunitario en la desnutrición

La desnutrición infantil puede afectar muchísimo al crecimiento y debilitar el sistema inmunitario, lo que hace que los niños sean más vulnerables a las infecciones y a la inflamación crónica. Hasta ahora, la mayoría de las intervenciones nutricionales no han logrado resultados satisfactorios. Nuevas investigaciones revelan que la exposición temprana a los microbios y virus del cuerpo, el microbioma y el viroma, tiene una gran importancia en la configuración del desarrollo inmunitario. En el proyecto Virome-SHIELD, que cuenta con el apoyo de las acciones Marie Skłodowska-Curie, se investigará la influencia de los virus presentes en el intestino en las respuestas inmunitarias, sobre todo en el contexto de la desnutrición. El equipo del proyecto empleará modelos murinos para estudiar cómo la exposición vírica temprana afecta al crecimiento, el metabolismo y el riesgo de enfermedad, con el objetivo de desarrollar terapias específicas para cada sexo que mejoren la salud de niños desnutridos en todo el mundo.

Objetivo

Nearly half of all deaths in children under five are linked to undernutrition, which causes developmental issues and increased susceptibility to infections and intestinal inflammation that are not fully corrected by traditional nutrition strategies. Early exposure to commensal bacteria shapes immune trajectories, influencing susceptibility to infections and inflammatory diseases both early in life and in the long-term. Reseach from the host laboratory has demonstrated that commensal bacteria contribute to host development, particularly under conditions of undernutrition. Similarly, commensal viruses (aka the virome) can modulate immune responses. Infants, especially in regions with high rates of undernutrition, are highly exposed to these viruses. However, the virome’s impact on immune development and its contribution to the effects of undernutrition remains largely unexplored. Building on my experience working with a commensal murine enteric virus, I aim to investigate how early immune imprinting by the virome alters host-development trajectories —including growth, metabolism, and sexual maturation—and affects long-term susceptibility to infections and inflammatory diseases in male and female mice. Using a combined approached of hypothesis-driven research (focusing on the homeostatic role of type I interferons) and a RNA sequencing-based discovery, this study will uncover unknown physiological functions of immune cells that are critical in challenging environments like undernutrition. The findings from this study will provide new insights into how understudied factors—such as the virome, sex, and undernutrition—affect immune function, including host-defenses and physiological functions. This knowledge could lead to innovative preventive and therapeutic strategies for undernourished children, such as microbiota-targeted food and immune-based interventions, tailored specifically for boys and girls.