The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts...

Area of Science:

• Immunology
• Pulmonology
• Microbiology

Background:

• Phagocytosis and inflammation are key to lung defense against bacterial pneumonia.
• The role of Triggering Receptor Expressed on Myeloid Cells-2 (TREM-2) in respiratory infections remains unclear.
• TREM-2 was previously thought to inhibit Toll-like receptor (TLR)-mediated responses and boost macrophage phagocytosis.

Purpose of the Study:

• To investigate the function of TREM-2 in the innate immune response to pneumococcal infection in the respiratory tract.
• To determine the presence and role of TREM-2 on alveolar macrophages (AMs) during bacterial pneumonia.

Main Methods:

• Establishing the presence of TREM-2 on alveolar macrophages (AMs).
• Comparing bacterial phagocytosis in TREM-2 deficient (Trem-2(-/-)) and wild-type (WT) AMs in vitro and in vivo.
• Analyzing pulmonary macrophage production of complement component 1q (C1q) and its dependence on peroxisome proliferator-activated receptor-δ (PPAR-δ).
• Assessing bacterial clearance, bacteremia, and survival rates in Trem-2(-/-) and WT mice infected with Streptococcus pneumoniae.

Main Results:

• TREM-2 deficient AMs showed enhanced bacterial phagocytosis compared to WT AMs.
• Pulmonary macrophages from Trem-2(-/-) mice produced elevated levels of C1q, dependent on PPAR-δ activity.
• These increased C1q levels were responsible for the augmented phagocytosis of bacteria.
• Trem-2(-/-) mice exhibited improved bacterial clearance from lungs, reduced bacteremia, and increased survival rates post-pneumococcal infection.

Conclusions:

• TREM-2 plays a previously unrecognized role in respiratory tract infections.
• Absence of TREM-2 leads to enhanced pulmonary macrophage phagocytosis via C1q production.
• This study reveals a novel link between TREM-2 and opsonin production in lung immunity, impacting host defense against pneumonia.