Abstracts (complete list) - Wissenschaft Online

Manuela Hessmann, Dominik Rueckerl, Toshiyuki Takai, Stefan Ehlers, Christoph
Hoelscher
The ITAM-bearing adapter protein DAP12 modulates
inflammatory immune responses after Mycobacterium
tuberculosis infection
Activation of the innate immune system leads to the release of pro-inflammatory
cytokines and is considered to be a prerequisite for driving a protective adaptive
immune response after infection. However, inflammatory immune responses may also
lead to tissue destruction and regulatory mechanisms are necessary to prevent
uncontrolled inflammation. Hence, activating and inhibitory host factors are required in
order to balance protection and immunopathology. When associated with different
receptors, the ITAM-containing signalling adaptor DAP12 (DNAX activating protein of 12
kDa) has been shown to affect inflammatory immune responses.
To analyse the influence of DAP12 on cell-mediated immune responses during
mycobacterial infection we infected DAP12-deficient (KO) mice with Mycobacterium
tuberculosis. In contrast to wildtype mice, infection of DAP12 KO animals resulted in
increased inflammatory immune response. In the absence of DAP12, the expansion of
activated T cells was enhanced accompanied with elevated antigen-specific effector
functions. On the cellular level, we could show that DAP12 KO macrophages
overproduce pro-inflammatory cytokines in response to M. tuberculosis infection.
In summary, we assume DAP12-dependent pathways in macrophages to modulate
inflammatory immune responses during mycobacterial infection. These signalling
pathway may represent novel target in order to mitigate chronic inflammation in human
tuberculosis.