Triggering receptor expressed on myeloid cells-1 (TREM-1) as a therapeutic target in infectious and noninfectious disease: a critical review

Abstract

The triggering receptor expressed on myeloid cells-1 (TREM-1) is an innate immune receptor found in the surface of several immune and non-immune cells. Since its first description in 2000, this molecule and its soluble form (sTREM-1) have been implicated in many diseases with infectious and noninfectious origins. As an amplifier of inflammation, the membrane-associated TREM-1 (mTREM-1) isoform induces the production of pro-inflammatory mediators, thus contributing to the pathogenesis of diseases such as sepsis, arthritis, colitis and infections. In this context, many studies have used molecules capable of inhibiting TREM-1 activity as anti-inflammatory drugs. In this regard, a few peptides have been showing promising results in the amelioration of detrimental immune responses. Some commercially available drugs, including corticosteroids and antibiotics, with known anti-inflammatory effects, have also shown activity in TREM-1 signaling. Therefore, considering the potential of this receptor as a therapeutic target, the present review encompasses the main compounds explored so far in TREM-1 modulation, highlighting and critically discussing its effects and major drawbacks of such approaches.