Decoding DAMPs Investigating the intricate crosstalk between host response and collateral damage

The innate immune system is able to rapidly respond to invading pathogens by virtue of its capacity to recognize conserved motifs expressed by microorganisms, named pathogen associated patterns (PAMPs). Innate immune cells sense PAMPs by a variety of pattern recognition receptors. Remarkably, many of these pattern recognition receptors can also recognize endogenous molecules. Under physiological conditions an interaction between host molecules and immune activating pattern recognition receptors is prevented by the fact that they do not reside in the same intra- or extracellular compartment or environment.
When the integrity of the cell is disrupted, which can be caused by anything ranging from burns, blunt trauma or inflammation, host endogenous molecules can become displaced and meet their recognizing receptors. These molecules then become so-called alarmins or damage associated molecular patterns (DAMPs). DAMPs can further activate the immune system to give rise to injurious inflammation.
In this thesis we studied several of these immune-system activating host molecules called DAMPs and their respective receptors. We documented the release of several DAMPs in the circulation during experimentally induced infection or inflammation and studied their cellular source and functional role in mice. We showed the relevance of these findings for humans by detecting DAMPs in plasma of healthy men injected with LPS and of patients with tuberculosis or sepsis. Considering the pleiotropic actions of DAMPs, the findings described in this thesis may add to a further understanding of the role of DAMPs in the immune response during infection, injury and inflammation.