TREM1 Blockade: Killing Two Birds with One Stone.

Area of Science:

• Neuroimmunology
• Inflammation research
• Microbiome-gut-brain axis

Background:

• Infectious and sterile injuries release pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).
• Stroke-induced sterile brain inflammation involves complex signaling pathways.
• The interplay between the nervous system, gut, and immune system is crucial in inflammatory diseases.

Purpose of the Study:

• To investigate the mechanisms linking DAMP-induced sterile brain inflammation in stroke to systemic responses.
• To explore the role of the sympathetic nervous system and gut permeability in stroke-related inflammation.
• To evaluate TREM1 as a potential therapeutic target for stroke and DAMP/PAMP-induced inflammation.

Main Methods:

• The study by Liu et al. (Nat. Immunol. 2019) investigated DAMP-induced sterile brain inflammation in a stroke model.
• Analysis included assessing sympathetic nervous system activation and its impact on intestinal permeability.
• Evaluation of microbiota-derived PAMPs and TREM1 involvement was performed.

Main Results:

• DAMP-induced sterile brain inflammation in stroke is associated with sympathetic nervous system activation.
• This activation enhances intestinal permeability, promoting the release of microbiota-derived PAMPs.
• TREM1 was identified as a key mediator in this inflammatory cascade.

Conclusions:

• Stroke-induced sterile brain inflammation has systemic consequences mediated by the gut.
• Sympathetic nervous system activation plays a critical role in exacerbating inflammation via the gut-brain axis.
• TREM1 presents a promising therapeutic target for mitigating stroke and DAMP/PAMP-driven inflammatory conditions.