TREM-1 deficiency can attenuate disease severity without affecting pathogen clearance.

Area of Science:

• Immunology
• Infectious Disease

Background:

• Triggering receptor expressed on myeloid cells-1 (TREM-1) amplifies pro-inflammatory innate immune responses.
• Excessive TREM-1 activity can lead to host damage, but its precise role in microbial control is debated.
• Previous studies used TREM-1 fusion proteins or peptides, potentially causing off-target effects.

Purpose of the Study:

• To unambiguously investigate the role of TREM-1 in immune homeostasis and disease.
• To determine if TREM-1 is required for effective microbial control.
• To assess the therapeutic potential of blocking TREM-1 in inflammatory disorders.

Main Methods:

• Generation of Trem1-deficient (Trem1(-/-)) mice.
• Induction of colitis using CD4(+) T cells and dextran sodium sulfate.
• Infection models including Leishmania major, influenza virus, and Legionella pneumophila.

Main Results:

• Trem1(-/-) mice showed significantly attenuated disease in colitis models with reduced inflammation and cytokine expression.
• TREM-1 deficiency led to reduced neutrophilic infiltration and smaller lesions in Leishmania major infections.
• Trem1(-/-) mice exhibited reduced morbidity during influenza virus infection.
• Despite reduced pathology, Trem1(-/-) mice effectively controlled L. major, influenza virus, and L. pneumophila infections.

Conclusions:

• TREM-1 has a pathogenic role in viral and parasitic infections, contributing to excessive inflammation.
• Therapeutic blockade of TREM-1 may reduce inflammation in certain disorders without compromising microbial clearance.
• TREM-1 deficiency offers a potential strategy for managing inflammatory diseases while maintaining host defense.