Seminars - Malaghan Institute of Medical Research

Asthma and Parasitic
Diseases
Clinical Perspective and Overview of Disease Project One: The Basic Biology of the Th2
Asthma is a chronic inflammatory disease of the airways
in the lungs characterised by periodic attacks of wheezing,
shortness of breath, chest-tightness, and coughing. It is
often triggered by harmless environmental stimulants
setting off the part of the immune response (termed
the Th2 immune response) that is normally involved in
protecting us against parasitic worms.
New Zealand has one of the highest prevalence rates of
asthma in the world; affecting one in six adults and one in
five children aged 6 to 14. Hospitalisation rates for asthma
sufferers have more than doubled in the past 30 years,
and the condition is conservatively estimated to cost
New Zealand approximately $825 million per year.
Although there are treatments available that reduce
the frequency and severity of asthma attacks, there is
currently no cure for this disease.
We hope that by researching the underlying mechanisms
of the Th2 immune response that gives rise to asthma,
we will obtain the knowledge and tools necessary for the
design of generally applicable vaccines and therapies for
the treatment of individuals with established disease.
Response
The cytokine interleukin-4 (IL-4) is thought to be critical
for the development of Th2 CD4+ T cells that respond to
parasitic infections and mediate allergic disease. We have
used genetically modified mice whose Th2 cells fluoresce
in a harmless way when they become active to quantify
the IL-4 dependency of the Th2 immune response to the
nematode parasite Nippostrongylus brasiliensis.
In 2006 we confirmed that IL-4 and STAT6, previously
thought to be essential for inducing a Th2 immune
response, were not required for Th2 development in our
asthma and allergy models. IL-4 and STAT6 are however
necessary for recruitment of inflammatory cells to the
lung. Contrary to recent theories, we also showed that IL-2
and STAT5a signalling does not lead to Th2 induction in vitro.
These data indicate that the differentiation of naïve CD4 T
cells to Th2 cells occurs entirely independently of IL-4
and STAT6, and that parasite and allergen challenges
induce novel pathways for the selective induction of Th2
immune responses.
Group Members
Prof Graham Le Gros, Mali Camberis, Marina Harvie, Melanie
Prout, Dr Debbie Scarlett (to May), Dr Bridget Stocker,
Shiau-Choot Tang, Nicholas van Panhuys