Abstracts (complete list) - Wissenschaft Online

Kai Zanzinger, Carola Schellack, Gernot Geginat, Adelheid Cerwenka
TREM-1 in infection and cancer
Cells of the innate immune system play an important role in the first line of defense
against bacteria and viruses. Their activation is controlled by different receptor families
including the Ig superfamily with both inhibitory and activating isoforms. Activating
isoforms deliver stimulatory signals by their association with transmembrane adapter
proteins bearing Immunoreceptor Tyrosine-based Activation Motifs (ITAM). DAP12 is
such an adapter protein that associates with several receptor molecules such as the
Triggering Receptor Expressed on Myeloid cells-1 (TREM-1).
In human and mice, TREM-1 is highly expressed on granulocytes. However, little is
known about the modulation of its expression on monocyte subpopulations in mice.
Blood of naïve mice comprises two subsets of monocytes: ‘resident’ (F4/80 + Gr-1 - CD62L -
CX3CR1 hi ) and ‘inflammatory’ monocytes (F4/80 + Gr-1 + CD62L + CX3CR1 lo ). In our study,
we analyzed TREM-1 expression on these monocyte subsets upon stimulation with Tolllike
receptor ligands, infection with L. monocytogenes and in different cancer models.
We show that in naïve mice TREM-1 is only detectable on ‘resident’ but not on
‘inflammatory’ monocytes. In contrast, TREM-1 is upregulated on the F4/80 + Gr-1 +
‘inflammatory’ monocyte subpopulation upon application of Toll-like receptor ligands
and in L. monocytogenes infection. In addition, also in different tumor models the
‘inflammatory’ monocyte subpopulation upregulates TREM-1. Interestingly, this
population in tumor-bearing mice is phenotypical and functionally identical to recently
described myeloid-derived suppressor cells (MDSC).
The future objectives of this project are to identify the factors that regulate TREM-1 on
this monocyte subpopulation in cancer.