Langhans giant cells in tuberculosis granulomas are formed by fusion of which cells, and what cytokine is critical for this fusion process?

• A Dendritic cells fuse under influence of IL-17A and TNF-alpha
• B Monocytes fuse under influence of M-CSF and RANKL
• C Epithelioid macrophages fuse under influence of IL-4 and GM-CSF ✓
• D Neutrophils fuse under influence of IL-8 and IFN-gamma

Explanation

Langhans giant cells are formed by fusion of activated epithelioid macrophages (macrophages that have undergone transformation under IFN-gamma stimulation, developing abundant cytoplasm with reduced phagocytic but enhanced secretory function). The peripheral arrangement of nuclei in a horseshoe pattern (Langhans type) is characteristic of TB granulomas. IL-4 and GM-CSF (granulocyte-macrophage colony-stimulating factor) are the primary cytokines that drive macrophage-macrophage fusion. IL-13 also promotes fusion. IFN-gamma is critical for epithelioid transformation and granuloma formation but IL-4/GM-CSF specifically mediate the multinucleation step. RANKL mediates osteoclast (bone-resorbing giant cell) formation, which is a distinct process. Dendritic cells and neutrophils do not form Langhans cells.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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