Abstracts (complete list) - Wissenschaft Online

Heiko Bruns, Frank Stegelmann, Steffen Stenger
Abl-tyrosine kinase modulates immune responses to
Mycobacterium tuberculosis
Tyrosine kinases are checkpoints for activation of cellular immune responses. We
hypothesized that Mycobacterium tuberculosis (M.tb.) interferes with tyrosine kinase
function to circumvent killing by the host cell.
We chose to focus on Abl (Abelson) - tyrosine kinase, because it is known to orchestrate
immune response to mycobacterial infection like proliferation, adhesion and apoptosis.
We measured TNF and IFN-gamma release by human PBMC in the presence of the
specific tyrosine kinase inhibitor STI-571. STI-571 treatment inhibited TNF and IFNgamma
release induced by mycobacterial antigens up to 90% (n=7). Furthermore
inhibition of Abl-tyrosine kinase influenced lymphocyte migration. The cell-migration
towards the chemokines CCL21 and CCL5, both required for the containment of
Mycobacterium tuberculosis in granulomas, were affected. Specifically, migration of
PBMC towards CCL21 was enhanced (three-fold), whereas movement towards CCL5 was
reduced.
These findings may be clinically relevant, because STI-571 (Imatinib) is a standard
treatment in chronic myeloid leukaemia. Deviation of cellular immunity as described
here may increase the risk for the occurrence of infectious diseases during Imatinib
therapy.