Origin and Development of the B cell response during Immunoregulatory Helminth Infections

Descrizione del progetto

La risposta delle cellule B durante le infezioni da elminti

Un quarto della popolazione mondiale viene infettato da vermi parassiti (elminti), che possono influenzare le risposte immunitarie a vaccini e infezioni. Pur sapendo che questi vermi possono indebolire il sistema immunitario, non è certo come influiscano sulla generazione di anticorpi protettivi da parte dei linfociti B. Il progetto B-SELECT, finanziato dal CER, mira a scoprire le modalità di formazione di specifiche cellule B e il modo in cui gli elminti ne compromettono lo sviluppo. Attraverso lo svolgimento di studi a livello molecolare, il progetto determinerà come le cellule B vengono attivate e selezionate durante le infezioni da elminti, offrendo risultati che dovrebbero chiarire il modo in cui aggirare l’interferenza causata dagli elminti e aiutare gli scienziati a progettare vaccini più efficaci.

Obiettivo

One-fourth of the global population is currently infected with helminths, which modulate host immunity against not only their own antigens but also non-cognate antigens, including vaccines. While antigen-specific antibodies and memory B cells are essential for protection against infectious diseases, how the B cell response quality is influenced by helminths remains largely unknown. With my core expertise in studying responses to parasites at the level of single B cells and monoclonal antibodies, I aim to delineate the onset and quality of B cell responses formed during immunoregulatory helminth infections, impacting the development of effective vaccines.
The B cell response quality relies on recruiting antigen-specific naïve cells and selecting high-affinity B cells to form antibody-secreting cells and memory B cells. However, how these well-established mechanisms are impaired during B cell immunity modulated by helminths remains unknown. Therefore, the goal of this ERC proposal is to elucidate the molecular principles governing the formation and selection of antigen-specific B cells during helminth-induced immunoregulation and to identify strategies to mitigate modulation.
To achieve this, I will investigate the origin and development of de novo helminth antigen-specific B cell responses in the unique controlled helminth infections in naïve individuals and vaccine-specific B cell responses in residents of helminth-endemic areas. Access to clinical samples, advanced human tonsil organoids and transgenic mouse models, combined with my state-of-the-art expertise in studying antigen-specific B cells, uniquely positions me to uncover paradigm-shifting molecular principles that guide B cell responses during helminth infections. Ultimately, I aim to provide the first proof of concept to mitigate modulatory effects and rescue B cell response quality, paving the way to address global health challenges by inducing protective vaccine response in helminth-infected individuals.