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

Description du projet

Développement immunitaire en cas de sous-alimentation

La dénutrition chez les enfants peut gravement nuire à leur croissance et affaiblir leur système immunitaire, les rendant plus vulnérables aux infections et aux inflammations à long terme. Jusqu’à présent, la plupart des solutions basées sur la nutrition sont souvent insuffisantes. La recherche montre aujourd’hui que l’exposition précoce aux microbes et aux virus de l’organisme - le microbiome et le virome - joue un rôle clé dans le développement du système immunitaire. Soutenu par le programme Actions Marie Skłodowska-Curie, le projet Virome-SHIELD explore la manière dont les virus présents dans l’intestin influencent les réponses immunitaires, notamment dans le contexte de la dénutrition. À l’aide de modèles de souris, le projet étudie comment l’exposition virale précoce affecte la croissance, le métabolisme et le risque de maladie, dans le but de mettre au point des thérapies sexospécifiques qui améliorent les résultats pour les enfants en état de malnutrition dans le monde.

Objectif

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.