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Modulation of neutrophil function by bioactive diets: impact on intestinal immunopathology

Carlsberg Foundation Visiting Fellowships at University of Oxford

What

Our intestinal tissue microenvironment is constantly challenged by environmental, microbial and dietary factors. Some dietary components, such as bioactive prebiotic fibres, are known to alter the intestinal microenvironment and interact with host immune and intestinal barrier cells. Innate immune processes, involving white blood cells such as neutrophils, are vital in maintaining our intestinal environment. Yet, there are still many unknowns regarding how specific dietary components precisely influence our innate-responding cells, such as neutrophils. This project aims to understand the mechanistic pathways by which dietary components, for instance prebiotic fibres, can modify host intestinal microenvironments and innate immune responses.

Why

Neutrophils are capable of traversing the intestinal barrier in response to microbial signals, and are essential for defending against pathogens. These cells are also central players for initiating inflammation at sites of infection, and have recently been shown to undergo functional changes as a result of infection-induced intestinal microenvironments. It is therefore plausible that diet-induced intestinal microenvironments may also alter functionality of neutrophils, which in turn may influence immune responsiveness during infection. Answering such questions will improve our understanding of the complex interactions between diet, host and pathogen infection, and potentially shed light on novel neutrophil signalling mechanisms.

How

This project will utilise in vitro culture systems to study the direct interactions between dietary components and neutrophils, with advanced transcriptomic analyses used to examine the diet-induced state of neutrophils both in vitro and in vivo. Furthermore, state-of-the-art imaging platforms will be employed to evaluate the functional characteristics of diet-modified neutrophils, and their interactions with the intestinal barrier during pathogen infection.

SSR

Understanding how diet influences and interacts with our immune cells and intestinal barrier is crucial for promoting health and preventing disease. This project will unravel the complex role of bioactive diets in shaping host immune responses in the intestinal tract. Moreover, we will gain fundamental insights into neutrophil biology and function, which will undoubtedly have wider reaching implications in the understanding of immunity to infection and induction of inflammation during chronic inflammatory diseases.