Completed Infection & Immunity Genetics & Molecular Biology

The role and modulation of Dectin-1 function in innate and adaptive immunity.

In plain English

AI plain-English summary

A receptor on the surface of immune cells, called Dectin-1, acts as a sensor for fungal invaders, and this project will determine exactly how it triggers the body's defences against infections like thrush and bloodstream infections caused by *Candida albicans*. Fungal infections are a major and growing threat, particularly for hospitalised or immunocompromised patients, yet the immune system's first line of defence against them remains poorly understood. Dectin-1 is the key receptor that recognises the sugar molecules in fungal cell walls, but scientists do not fully know how its genetic variations affect a person's susceptibility to infection, nor how it influences antibody production by B-cells. This project will fill those gaps by studying human cells with different Dectin-1 gene variants, mapping the signalling pathways it activates, and testing whether purified beta-glucans—the sugars it detects—can be used as vaccine adjuvants to boost immune responses. If successful, the work could lead to better risk assessment for patients prone to fungal infections and open the door to new therapeutic strategies that harness Dectin-1 to fight not just fungi but other pathogens. The research is fundamentally curiosity-driven, but understanding this receptor's role in shaping adaptive immunity could eventually translate into improved vaccines or immune-modulating drugs.

View original technical description
Dectin-1 is a signalling pattern recognition receptor that recognises fungal cell wall beta-glucans, inducing a variety of cellular responses and the development of adaptive immunity. Here I propose to examine the role of Dectin-1 in innate and adaptive anti-fungal immunity, and to understand and utilise the ability of this receptor to modulate immune responses. I will focus on the role of Dectin-1 in immunity to Candida albicans, one of the most prevalent infectious agents of man, but will also look at its involvement in driving immune responses to other selected fungal pathogens. The consequence of polymorphisms on Dectin-1 function will be examined in humans, and related to susceptibility to infection. The role of Dectin-1 on human B-cells will be explored, and its effects on humoral immunity. Novel insights into the effects of Dectin-1 mediated signalling will be obtained using microarrays. The protective mechanisms induced through Dectin-1 by purified beta-glucans will be examined using infection models, and the use of these carbohydrates as adjuvants will be explored. These studies will greatly advance our understanding of the role of Dectin-1 in immunity, and will provide crucial insights to the applicability of this receptor as a therapeutic target.

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Researchers

Gordon Brown (EPMC Awardee)

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Original classification

Programme Grant

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