Frank van de Veerdonk wins Veni award

Veerdonk Frank van de
Frank van de Veerdonk (Department of General Internal Medicine) has been awarded a Veni grant to study host defence against Gram-positive bacteria and fungal pathogens.

Cytokines of the innate immunity, in particular the IL-1 family (IL-1F) members IL-1b and IL-18, play a major role in modulating T-helper responses in host defence. Novel members of the IL-1F have recently been described, but their role in modulation of adaptive immunity is unknown. The aim of the present proposal is to investigate the capability of the IL-1F members IL-36a, IL-36b, IL-36g (with proinflammatory activity), and IL-36Ra, IL-37 (with anti-inflammatory activity) to polarise T-helper responses during infection. Based on preliminary data, I hypothesise that the novel IL-1F members predominantly modulate Th17 responses, and thus are essential for the host defence against Gram-positive bacteria and fungal pathogens.

Three key objectives will be pursued:
1. To identify the function of the new IL-1F members for T-helper responses in vitro. Human and murine immune cells will be exposed to various IL-1F cytokines and T-helper responses will be investigated. In addition, endogenous IL-1F cytokines will be blocked with specific antibodies or siRNA, and cells from IL-37-transgenic and IL-1RL2-deficient (receptor for IL-36a,b,g) mice will be studied.
2. To decipher the role of IL-1F members in regulating T-helper responses during infections in vivo.
Wild-type, IL-37-transgenic, and IL-1RL2-deficient mice will be infected with Streptococcus pneumoniae or Candida albicans to decipher the importance of IL-1F members in regulating T-helper responses during infection. 3. To investigate the role of IL-1F cytokines in patients with an inappropriate Th17 response, and in patients with bacterial and fungal infections.

The role of IL-1F cytokines in patients with chronic mucocutaneous candidiasis and hyper-IgE syndrome will be studied. In addition, genetic polymorphisms in IL-1F members will be assessed in cohorts of patients with bacterial sepsis or disseminated candidiasis. These studies will provide crucial information to assess feasibility to design new therapeutic approaches against bacterial and fungal infections based on the novel IL-1F members.

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