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Pathogens, on the other hand, have developed countermeasures to enable their replication and spreading. For intracellular pathogenic bacteria, the battleground is localized at the cellular level. Different cell types, including phagocytic, epithelial, and endothelial cells, fibroblasts, and trophoblasts, not only are equipped with diverse defense tools, but also provide different microenvironments, such as varying oxygen tension, pH levels, tonicity, and nutrient supply. The outcome of the infection depends on these conditions in conjunction with microbe-derived virulence factors and bacterial microenvironment needs. Here, we will review the current knowledge on how eukaryotic cells fight obligate intracellular bacteria and how these pathogens counteract the host cell defenses, focusing on cell death pathways. 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