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TREM Receptors Connecting Bowel Inflammation to Neurodegenerative Disorders

1
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56100 Pisa, Italy
2
I.R.C.C.S Neuromed, Via Atinense 18, 86077 Pozzilli, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(10), 1124; https://doi.org/10.3390/cells8101124
Received: 30 August 2019 / Revised: 16 September 2019 / Accepted: 21 September 2019 / Published: 21 September 2019
Alterations in Triggering Receptors Expressed on Myeloid cells (TREM-1/2) are bound to a variety of infectious, sterile inflammatory, and degenerative conditions, ranging from inflammatory bowel disease (IBD) to neurodegenerative disorders. TREMs are emerging as key players in pivotal mechanisms often concurring in IBD and neurodegeneration, namely microbiota dysbiosis, leaky gut, and inflammation. In conditions of dysbiosis, compounds released by intestinal bacteria activate TREMs on macrophages, leading to an exuberant pro-inflammatory reaction up to damage in the gut barrier. In turn, TREM-positive activated macrophages along with inflammatory mediators may reach the brain through the blood, glymphatic system, circumventricular organs, or the vagus nerve via the microbiota-gut-brain axis. This leads to a systemic inflammatory response which, in turn, impairs the blood-brain barrier, while promoting further TREM-dependent neuroinflammation and, ultimately, neural injury. Nonetheless, controversial results still exist on the role of TREM-2 compared with TREM-1, depending on disease specificity, stage, and degree of inflammation. Therefore, the present review aimed to provide an update on the role of TREMs in the pathophysiology of IBD and neurodegeneration. The evidence here discussed the highlights of the potential role of TREMs, especially TREM-1, in bridging inflammatory processes in intestinal and neurodegenerative disorders. View Full-Text
Keywords: dysbiosis; microbiome; inflammatory bowel disease; gut-brain-axis; neurodegeneration; TREM-1; TREM-2; myeloid-derived cells; autophagy dysbiosis; microbiome; inflammatory bowel disease; gut-brain-axis; neurodegeneration; TREM-1; TREM-2; myeloid-derived cells; autophagy
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Natale, G.; Biagioni, F.; Busceti, C.L.; Gambardella, S.; Limanaqi, F.; Fornai, F. TREM Receptors Connecting Bowel Inflammation to Neurodegenerative Disorders. Cells 2019, 8, 1124.

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