
-   TREM-2 activates the DNAX-activating protein of 12 kDa (DAP12) adaptor protein and negatively regulates TLR signaling in macrophages and dendritic cells and reduces the inflammation response [PMID: 16951310, PMID: 16887962].
-   TREM-2 is a is a phagocytic receptor for bacteria and promotes clearance of bacteria [PMID: 19171755, PMID: 12847223]. TREM2-knockout mice showed exacerbated lung inflammation after bacterial infection [PMID: 25477281, PMID: 33863908].
-   TREM2 deletion enhances macrophage activation and accelerates the elimination of mycobacterial infection, suggesting that TREM2-DAP12 signaling counteracts anti-mycobacterial immunity [PMID: 33863908].
-   Knockdown of TREM2 suppresses pulmonary fibrosis, which may be associated with reduced infiltration of M2 macrophages [PMID: 37003186].

## Summary

TREM2 enhances the phagocytic activity of both microglia in the brain and macrophages in peripheral tissues, including the lung, contributing to the functional removal of cellular debris and potentially limiting the release of pro-inflammatory cytokines indirectly through these phagocytic processes. TREM2's capacity to bind anionic phospholipids like phosphatidylserine, a component of cell membranes typically exposed on the surface of apoptotic cells, facilitates the recognition and ingestion of these cells by immune cells. The recognition and management of such phospholipids via TREM2 thus plays an instrumental role in maintaining pulmonary surfactant homeostasis, particularly under conditions of lung injury where disrupted alveolar cells might otherwise accumulate and impair gas exchange.

In lung diseases, such as COPD, IPF, and in response to bleomycin or ovalbumin challenge, TREM2 upregulation plays a key role in the recruitment and activation of immune cells that attempt to remove cellular debris and manage inflammation, part of an innate response to lung injury. This upregulated expression of TREM2 correlates with decreased lung function and negative clinical outcomes, likely because the enhanced immune response and macrophage activity could contribute to further inflammation and tissue damage when not properly resolved. In the case of bacterial infections in the lung, TREM2 aids in the clearance of bacteria, and its absence exacerbates inflammation, indicating that TREM2's function is crucial for resolving infections and minimizing tissue damage.
