Effects of dietary fatty acids on macrophage organelle function
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Asthma
Fatty acid
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Abstract
Immune cells work together to locate, identify, and clear bacteria, viruses, and substances that appear foreign and harmful. Dysregulation of immune cells in the lung can result in inflammatory pathologies, such as asthma and severe viral infections. Macrophages are a type of white blood cell of the innate immune system that perform phagocytosis to kill microorganisms, remove dead cells, and stimulate the action of other immune system cells. Phagocytosis involves cell surface molecules recognizing the target, then the cell engulfs the target. Within the macrophage, acidic compartments break down the consumed target. Macrophages in the lung exhibit perturbed functions in lung pathology, such as altered metabolism and inhibited clearance of dead cells. Dietary elements may contribute to these perturbations. For example, obesity is associated with both heightened inflammation and increased incidence of bronchial asthma, a chronic lung disease affecting individuals of all ages. It is unclear how diets associated with obesity lead to changes in lung immune function. Notably, the Western diet is characterized by a high intake of processed and refined foods as well as red and processed meats that contain abundant saturated long-chain fatty acids, namely the 18-carbon stearic acid. The Hill lab has reported that stearate enrichment in primary macrophage media (in vitro) and in the diet (in vivo) induces pro-inflammatory signaling and transcriptional shifts in macrophages that contribute to worsened lung function in an asthma model (McCright et al., Science Translational Medicine, in press). In the proposed research, I will investigate how stearate affects macrophage phagocytosis.