SPIC-dependent erythrophagocytic macrophages drive granuloma formation and pathogen persistence during intracellular...

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Macrophages are crucial for tissue homeostasis and host defense but can also harbor intracellular pathogens.
• Granulomas are organized structures that can promote pathogen persistence, such as with Salmonella enterica.

Purpose of the Study:

• To investigate the role of SPIC in macrophage function during Salmonella Typhimurium infection.
• To elucidate the mechanisms by which granulomas form and support bacterial persistence.

Main Methods:

• Utilized a murine Salmonella Typhimurium infection model.
• Employed CRISPR gene editing to generate SPIC-deficient mice.
• Analyzed macrophage populations, including VCAM1+ macrophages, and their functions (e.g., erythrophagocytosis, co-stimulatory ligand expression).

Main Results:

• Granuloma formation and Salmonella persistence were dependent on SPIC.
• SPIC controls the development of VCAM1+ macrophages involved in erythrocyte, heme, and iron recycling.
• SPIC deficiency impaired macrophage co-stimulatory ligand expression and the formation of a VCAM1+ macrophage zone that retains T cells.
• SPIC deletion reduced bacterial persistence and altered granuloma cellular architecture.

Conclusions:

• SPIC is a critical regulator of granuloma formation and bacterial persistence.
• SPIC-dependent VCAM1+ macrophages play a key role in driving granuloma development and enabling intracellular bacterial survival.