Abstract
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.
Highlights
Macrophages play a key role as the front line of host defenses against foreign bodies
Each pathogen has evolved its own strategy to thrive in or kill the host cells, and it is not surprising to find that a single lipid class or species can display contrasting functions during bacterial infections, depending on the bacterial species and even cell types
A single lipid, such as cholesterol, can be utilized by a specific pathogen to promote its own survival in the macrophage and on the other hand, it can be used by the host to assist in clearance of another bacterial species, making lipids a double-edge sword in the complex host–pathogen relationship
Summary
Macrophages play a key role as the front line of host defenses against foreign bodies. The inflammatory and anti-inflammatory responses of macrophages are tightly regulated at different infection stages and are pathogen-specific Disturbance in this equilibrium will lead to excessive inflammation, or failure to activate the immune response, and this is often exploited by pathogens through the hijack of host signaling mechanisms to evade clearance by professional phagocytes. Lipids are fundamental building blocks of cells and play pivotal roles in diverse biological processes They are key structural components for cellular membranes. Lipids serve as energy stores in eukaryotic cells, in the form of triglyceride esters and steryl esters in lipid droplets They play a key role as first and second messengers in signaling cascades. It should be noted that this is not exhaustive as many other pathogens, including eukaryotic parasites, viruses, and fungal pathogens are capable of manipulating host lipid metabolism as part of their survival strategies [8, 9, 16, 17]
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