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

Descrizione del progetto

Lo sviluppo immunitario in condizioni di denutrizione

La denutrizione nei bambini può compromettere seriamente la crescita e indebolire il sistema immunitario, rendendoli più vulnerabili alle infezioni e alle infiammazioni a lungo termine. Sino ad ora, la maggior parte delle soluzioni basate sulla nutrizione sono risultate spesso insufficienti. Le ricerche dimostrano che l’esposizione precoce ai microbi e ai virus dell’organismo, ovvero il microbioma e il viroma, svolge un ruolo fondamentale nel plasmare lo sviluppo immunitario. Sostenuto dal programma di azioni Marie Skłodowska-Curie, il progetto Virome-SHIELD esplora le modalità attraverso cui i virus presenti nell’intestino influenzano le risposte immunitarie, soprattutto nel contesto della denutrizione. Utilizzando modelli murini, il progetto studia il modo in cui l’esposizione virale precoce influisce sulla crescita, sul metabolismo e sul rischio di malattia, con l’obiettivo di sviluppare terapie specifiche a livello di genere che migliorino gli esiti clinici dei bambini sottonutriti a livello globale.

Obiettivo

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.