Immunology research update from www.immunopaedia.org.za
n a new study from Nature Communications, Mistry, et al., have reported on how our immune cells use Free Fatty-acid (FFA) transport to fight infection. These insights could help develop new methods of treating bacterial infections. Acute infection is known to induce rapid expansion of hematopoietic stem cells (HSCs), but the mechanisms supporting this expansion remain incomplete.
Through investigation using Salmonella typhimurium, the researchers went on to track fatty acid movement and consumption in live hematopoietic stem cells (HSCs) (Figure 1). They analysed the immune response through analysis of liver damage. It was reported that HSCs recruit high energy free fatty-acids from the body’s fat stores in order to combat infection. The team found that in the bone marrow where blood stem cells are resident, infection signals drive adipocytes to release their fat stores as fatty acids into the blood. HSCs make use of FFAs by means of energy transfer, using the fatty-acids to produce lymphocytes geared towards combatting infection.
The researchers were also able to identify a mechanism by which the fatty acids are transferred, regulated and utilised (Figure 2). When our bodies are fighting infection, this requires significant amounts of energy and fat stores are huge energy deposits, which can provide fuel for the blood stem cells to use in the immune response.
In short, through the use of mouse models, they were able to show that inducible CD36 is required for free fatty acid uptake by HSCs during acute infection, allowing the metabolic transition from glycolysis towards β-oxidation.
In their own words:
“In conclusion, we report that adaptations in FFA uptake and FAO functionally support the hematopoietic response to bacterial infection. Furthermore, in doing so we provide a base for further studies investigating how benign and malignant stem cells in other tissues utilize FFA in response to cellular stress, and specifically whether the provision of FFA by adipocytes in the physiologic response to infection, is altered in individuals with particular vulnerabilities with respect to infection, including older people and those with obesity.”
Journal article: Mistry, et al., 2021. Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection. Nature Communications.