GM-CSF and M-CSF driven differentiation differentially regulates Chikungunya virus infection and antiviral responses in human monocyte-derived macrophages.

GM-CSF-differentiated human monocyte-derived macrophages are highly permissive to Chikungunya virus replication, while M-CSF-differentiated macrophages restrict CHIKV and show no detectable viral protein expression.

• Why it matters: Macrophages may both harbor persistent viral material and shape immunopathology, but how GM-CSF versus M-CSF differentiation alters CHIKV susceptibility and antiviral signaling is unclear.
• What they did: In parallel donor-matched primary macrophage cultures, cells were differentiated with GM-CSF or M-CSF and then infected with CHIKV (and Mayaro virus), with antiviral cytokines/chemokines measured after infection or stimulation with poly(I:C) versus R848.
• The result: CHIKV infection induced pro-inflammatory, M1-skewing in both differentiation states, but M-CSF macrophages produced higher IFNα and IP10/CXCL10, and poly(I:C) (not R848) recapitulated the antiviral response, implicating dsRNA sensing.

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