TREM receptors in infection and inflammation

The general aim of this thesis is to increase our insight in the immunopathogenesis of pulmonary inflammatory responses during bacterial infection and allergic lung responses with a focus on fine-tuning of innate immune responses by TREM-1 and TREM-2.
In sharp contrast to what is known about the role of TREM-1 in systemic inflammation, we here show that TREM-1 serves a protective role during both gram-positive and gram-negative pneumonia, while worsening disease outcome during allergic lung inflammation. TREM-2 on the other hand impairs host defense during gram-negative pneumonia and has no role in allergic airway inflammation. These results illustrate the complex nature of innate immunity, which in the initial phase of localized infection is essential for an adequate response to invading bacteria but during exaggerated inflammation elicited by high bacterial loads or during sustained allergic inflammation can contribute to collateral damage and tissue injury. While TREM receptors might serve as potential targets for the treatment of inflammatory diseases one must keep in mind there is a fine line between mitigating excessive inflammation and making the immune response ineffective.