Macrophage origin limits functional plasticity in helminth-bacterial co-infection

Area of Science:

• Immunology
• Cell Biology

Background:

• Macrophage phenotype reprogramming is vital for fighting infections.
• The roles of resident macrophage adaptation versus new cell recruitment in chronic infections are unclear.

Purpose of the Study:

• To investigate the functional importance of resident peritoneal macrophage adaptation versus monocyte recruitment during chronic infection.
• To compare the responses of nematode-expanded resident macrophages and newly recruited macrophages to Salmonella Typhimurium.

Main Methods:

• Used a co-infection model with Heligmosomoides polygyrus and Salmonella Typhimurium in mice.
• Analyzed macrophage activation phenotypes (F4/80high vs. F4/80low) using in vitro and in vivo assays.
• Performed global gene expression analysis to compare macrophage functional capabilities.

Main Results:

• Nematode-expanded resident macrophages upregulated bacterial-induced effector molecules but showed a muted anti-bacterial response compared to new recruits.
• New monocyte-derived macrophages were recruited equally in co-infected animals and displaced resident macrophages.
• Resident macrophages exhibited unique functions, including enhanced neutrophil-stimulating chemokine production.

Conclusions:

• Macrophage activation plasticity occurs in vivo during chronic infection.
• Cellular plasticity of resident macrophages is outweighed by functional capabilities inherent to their tissue of origin.
• Both resident macrophage adaptation and new cell recruitment contribute to the immune response, with distinct functional outcomes.