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Pauline van de Weert-van Leeuwen

Wednesday 18 September 2013

Rift Valley fever virus Glycoproteins, Key to Entry and Control

Promotor: Prof. dr. C.K. van der Ent
Defence: 18 September 2013

In this thesis, we investigated the association between exercise, infection and inflammation in patients with CF, since they have been described to be interconnected. Patients with CF spend a lot of time in physical exercise to maintain physical fitness, since exercise capacity declines during lifespan and has been described to be a good predictor of morbidity and mortality. However, this thesis shows that regular physical exercise not always leads to improvements of physical fitness in adolescents with CF and maybe even enhances susceptibility for pulmonary infections with P. aeruginosa in some patients.

The main findings of this thesis are:
Exercise capacity of adolescents with CF is comparable to that of age-matched healthy controls at the age of 12 years old, however it declines with 20% during adolescence.
P. aeruginosa colonization and IgG levels negatively affect the exercise capacity in adolescents with CF, independent of pulmonary function and nutritional status.
A reduced exercise capacity associates with higher mortality, a steeper decline in pulmonary function and a higher increase in IgG levels in adolescents with CF.
Exercise training responses are negatively associated with P. aeruginosa colonization and IgG levels in adolescents with CF.
Regular exercise increases susceptibility to pulmonary P. aeruginosa infection in mice without affecting innate phagocytic function.
CFTR is expressed in peripheral blood mononuclear cells, but not or only limited in neutrophils.
CFTR regulates optimal complement-mediated phagocytosis and killing of P. aeruginosa by monocytes, but not neutrophils