TREM-2: friend or foe in infectious diseases?

The triggering receptor expressed on myeloid cells-2 (TREM-2) is an immune receptor expressed on immune and non-immune cells, more frequently investigated in neurodegenerative disorders and considered a marker for microglia activation. In infectious diseases, the receptor was initially believed to be an anti-inflammatory molecule, opposing the inflammation triggered by TREM-1. Currently, TREM-2 is associated with different aspects in response to infectious stimuli, including the induction of bacterial phagocytosis and clearance, containment of exacerbated pro-inflammatory responses, induction of M2 differentiation and activation of Th1 lymphocytes, besides of neurological damage after viral infection. Here, we present and discuss results published in the last two decades regarding the expression, activation and functions of TREM-2 during the course of bacterial, viral, fungal and parasitic infections. A surprisingly plasticity was observed regarding the roles of the receptor in the aforementioned contexts, which largely varied according to the cell/organ and pathogen type, besides influencing disease outcome. Therefore, our review aimed to critically overview the role of TREM-2 in infectious diseases, highlighting its potential to be used as a clinical biomarker or therapeutic target.

TREM-1 isoforms in bacterial infections: to immune modulation and beyond.

The triggering receptor expressed on myeloid cells 1 (TREM-1) is an innate immunity receptor associated with the amplification of inflammation in sterile and non-sterile inflammatory disorders. Since its first description, the two isoforms of the receptor, membrane and soluble (mTREM-1 and sTREM-1, respectively) have been largely explored in the immunopathogenesis of several bacterial diseases and sepsis. The role of the receptor in these scenarios seems to be at least partly dependent on the source/type of bacteria, host and context. As uncontrolled inflammation is a result of several bacterial infections, the inhibition of the receptor has been considered as a promising approach to treat such conditions. Further, sTREM-1 has been explored as a biomarker for diagnosis and/or prognosis of several bacterial diseases. Therefore, this review aims to provide an updated insight into how the receptor influences and is influenced by bacterial infections, highlighting the advances regarding the use/manipulation of TREM-1 isoforms in biomedical research and clinical practice.

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

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.