TREM-1 amplifies inflammation and is a crucial mediator of septic shock

Area of Science:

• Immunology
• Microbiology
• Pathology

Background:

• Innate immunity relies on neutrophils and monocytes/macrophages expressing pattern recognition receptors (PRRs).
• PRR stimulation triggers pro-inflammatory mediators crucial for pathogen elimination and tissue repair.
• Excessive inflammation during bacterial infections can cause tissue damage and septic shock.

Purpose of the Study:

• To investigate the role of triggering receptor expressed on myeloid cells-1 (TREM-1) in amplifying inflammatory responses to microbial products.
• To evaluate TREM-1 as a potential therapeutic target for septic shock.

Main Methods:

• Assessed TREM-1 expression on neutrophils and monocytes in infected tissues and sepsis patients.
• Utilized mouse models of lipopolysaccharide (LPS)-induced shock and bacterial sepsis (E. coli, cecal ligation and puncture).
• Investigated the effect of TREM-1 blockade on survival and disease severity in these models.

Main Results:

• TREM-1 is highly expressed on neutrophils and monocytes infiltrating infected tissues.
• TREM-1 is upregulated on neutrophils in patients with microbial sepsis and in mouse models of shock.
• Blocking TREM-1 significantly protected mice against LPS-induced shock and polymicrobial sepsis.

Conclusions:

• TREM-1 plays a critical role in amplifying acute inflammatory responses to bacterial infections.
• TREM-1 is implicated as a key mediator in the pathogenesis of septic shock.
• Targeting TREM-1 represents a promising therapeutic strategy for managing septic shock.