TREM2 drives monocyte-derived macrophage responses to Cryptococcus neoformans

Area of Science:

• Immunology
• Mycology
• Infectious Diseases

Background:

• Cryptococcus neoformans causes serious infections.
• DAP12 signaling worsens host survival during cryptococcosis.
• Mechanisms initiating DAP12 signaling in cryptococcosis are unclear.

Purpose of the Study:

• Identify the DAP12-associated receptor initiating signaling during C. neoformans infection.
• Elucidate the role of this receptor in macrophage response and host immunity.

Main Methods:

• Investigated TREM2 expression on murine monocytes and macrophages during C. neoformans infection.
• Assessed the impact of TREM2 on fungal uptake and macrophage polarization.
• Utilized in vitro binding assays to study TREM2-fungal interactions.

Main Results:

• TREM2 is induced on lung macrophages in response to C. neoformans.
• TREM2 signaling inhibits fungal uptake and M1 polarization by macrophages.
• TREM2 directly binds C. neoformans, dependent on the β-1,6-glucan antigen.

Conclusions:

• The TREM2-DAP12 pathway inhibits host immune response to C. neoformans.
• TREM2 acts as a direct sensor for C. neoformans, impeding macrophage activation and phagocytosis.