Macrophages Recycle Bacterial Nutrients to Boost Immunity and Control Inflammation.

When microbes invade the human body, macrophages — a type of phagocytic immune cell — swiftly respond by capturing and digesting the intruders. Extending arm-like projections, they engulf the microbes into vesicles, initiating degradation. While the process of phagocytosis is vital for clearing pathogens, the fate of the ingested microbes within these vesicles has long remained unclear.

Johan Garaude, an immunologist at France’s National Institute of Health and Medical Research (INSERM), sought to answer whether the contents of these vesicles could also fuel macrophage metabolism. His team’s recent study, published in Nature, shows that macrophages can indeed extract nutrients from engulfed bacteria to meet their energy needs — a recycling process that varies depending on whether the bacteria are alive or dead.

During infections, bacteria often deprive host cells of essential nutrients. Garaude suggested that macrophages have evolved the ability to compensate by metabolizing the bacteria they engulf. "Macrophages probably developed this capacity to feed themselves with phagocytosed bacteria," he explained.

Andrea Wolf, an innate immunologist at Cedars-Sinai Medical Center who was not involved in the research, noted that phagocytosis has evolutionary roots as a nutrient acquisition method in single-celled organisms like amoebas.

To explore this metabolic recycling, Garaude’s team treated cultured macrophages with killed Escherichia coli (E. coli) cells. They observed increased expression of mitochondrial genes linked to ion transport and a higher oxygen consumption rate, indicating that bacteria-derived nutrients feed the mitochondrial respiratory chain.

Using dead E. coli labeled with heavy carbon isotopes, the researchers traced the carbon into macrophage metabolites such as glutathione — an antioxidant with anti-inflammatory properties. Further experiments in mice confirmed that macrophages recycle nutrients from engulfed bacteria in living organisms.

Focusing on the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which regulates cell metabolism, the team found that blocking mTORC1 in macrophages enhanced bacterial nutrient catabolism and boosted glutathione production. Conversely, activating mTORC1 reduced nutrient recycling, showing that this pathway controls how macrophages process phagocytosed material.

Intriguingly, the team discovered that macrophages responded differently depending on whether the engulfed bacteria were alive or dead. Dead bacteria triggered higher antioxidant production and the release of an immunomodulatory metabolite, partly because they contained 3′,5′-cyclic adenosine monophosphate (cAMP). Upon ingestion, cAMP byproducts suppressed mTORC1 activity, enhancing antioxidant defenses and dampening inflammatory responses.

Wolf remarked that while differences between live and dead bacterial handling were expected, it remains to be seen whether timing or recognition mechanisms account for the variations. She emphasized the potential of leveraging this response to control inflammation.

“This study opens a promising new direction in understanding how metabolism can aid in fighting bacterial infections,” said Garaude, highlighting the therapeutic possibilities ahead.

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Source:https://www.the-scientist.com/microbes-fuel-the-immune-cells-that-engulf-them-72947

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