FIGURE 5: The DNA damage response may control multinucleated macrophage cell fitness. (A) In osteoclasts RANK (Receptor Activator of NF-κB) signaling activates the NFκB (nuclear factor 'kappa-light-chain-enhancer' of activated B-cells) pathway promoting survival, an effect inhibited by ATM, leading to increased apoptosis. (B) Chronic bacterial infection and TLR2 ligands upregulate c-MYC and induce replication stress, which causes cytokinesis failure. ATR promotes growth, survival and genomic stability of polyploid macrophages in granulomatous microenvironments.