Abstracts (complete list) - Wissenschaft Online

Alexander Donald McLellan, Patrizia Stoitzner, Jacquie Harper, Sarah Saunderson,
Ralph Jack, Anthea Bouwer
Activation of natural killer cells by dendritic cells stimulated
with gram positive bacteria
Interferon-gamma (IFNγ) release by natural killer (NK) cells plays a key role in the
resolution of cancer or viral infection. We have previously shown that the cell wall
components of Gram-positive bacteria stimulate a rapid release of IFNγ from human and
murine leukocytes. The effect has also been found to be mimicked by the cell wall
component lipoteichoic acid (LTA) but not by other Toll-like receptor-agonists. NK cell
activation requires membrane-contact with bacteria-stimulated dendritic cells (DC), but
is independent of the adhesion molecule LFA-1 and the NK cell activation molecule
NKG2D. IL-12 and IL-18 expression was found to be essential for NK cell activation.
Activation of DC/NK with whole bacteria was maintained in TLR2-/- and TLR4-/-
backgrounds, however the stimulation of DC/NK with the cell wall component LTA was
lost in the TLR4-/- background, further fuelling the controversy surrounding the role of
this TLR in the recognition of Gram-positive bacteria. Despite inducing potent cytokine
secretion in DC/NK cells, Gram-positive cell wall stimulation did not lead to increased
natural or antibody-dependent (ADCC) cytotoxicity of NK cells against the NK-sensitive
target YAC-1 or antibody sensitised A20 cells. We are currently investigating the in vivo
potential of these adjuvants to drive NK cell activation and Th1 polarisation for the
treatment of tumours or infectious diseases.