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Macrophages are professional phagocytes at the front line of immune defenses against foreign bodies and microbial pathogens. Various bacteria, which are responsible for deadly diseases including tuberculosis and salmonellosis, are capable of hijacking this important immune cell type and thrive intracellularly, either in the cytoplasm or in specialized vacuoles. Tight regulation of cellular metabolism is critical in shaping the macrophage polarization states and immune functions. Lipids, besides being the bulk component of biological membranes, serve as energy sources as well as signaling molecules during infection and inflammation. With the advent of systems-scale analyses of genes, transcripts, proteins, and metabolites, in combination with classical biology, it is increasingly evident that macrophages undergo extensive lipid remodeling during activation and infection. Each bacterium species has evolved its own tactics to manipulate host metabolism toward its own advantage. Furthermore, modulation of host lipid metabolism affects disease susceptibility and outcome of infections, highlighting the critical roles of lipids in infectious diseases. Here, we will review the emerging roles of lipids in the complex host–pathogen relationship and discuss recent methodologies employed to probe these versatile metabolites during the infection process. An improved understanding of the lipid-centric nature of infections can lead to the identification of the Achilles’ heel of the pathogens and host-directed targets for therapeutic interventions. Currently, lipid-moderating drugs are clinically available for a range of non-communicable diseases, which we anticipate can potentially be tapped into for various infections.

Macrophage–Bacteria Interactions—A Lipid-Centric Relationship