The C3-C3aR axis modulates trained immunity in alveolar macrophages.

C3-C3aR signaling enhances trained immunity in alveolar macrophages, with C3 deficiency impairing cytokine production and metabolic activity in mice.

• Why it matters: Understanding how the complement system influences innate immune memory is vital for developing therapies for respiratory infections and inflammatory diseases, yet its role remains unclear.
• What they did: The study examined C3 and C3aR expression in human alveolar macrophages after nasal exposure and used wild-type and C3-deficient mice to assess immune responses, cytokine production, and metabolism, employing live microscopy and biochemical assays.
• The result: Findings show C3 and C3aR are essential for trained immunity, with C3 restoring cytokine and metabolic functions via C3aR engagement, revealing a novel immune regulatory pathway in lung macrophages.