If you’re a bacterium, lipid droplets afloat in a host cell’s cytoplasm may not look especially threatening. In fact, they may look as though they’re waiting to be foraged. But a new study reveals that lipid droplets form a first-line intracellular defense. They may be booby-trapped. Also, they may organize and support intracellular immune responses.

These findings, which were uncovered by researchers from the University of Queensland and the University of Barcelona, appeared in Science, in an article titled, “Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense.”

“It was previously thought that bacteria were merely using the lipid droplets to feed on,” said Robert Parton, PhD, a corresponding author of the article and a professor of cell biology and molecular medicine at the University of Queensland. “But we discovered that these fatty droplets are involved in the battle between the pathogens and our cells.

“Fat is part of the cell’s arsenal—cells manufacture toxic proteins, package them into the lipid droplets, then fire them at the intruders. This is a new way that cells are protecting themselves, using fats as a covert weapon, and giving us new insights into ways of fighting infection.”

To evaluate the role of mammalian lipid droplets in immune defense, the scientists used liver cells in mice and a proteomic approach. The scientists observed that when the lipid droplets were exposed to the bacterial toxin lipopolysaccharide, the lipid droplet proteome within the threatened cells changed. Lipid droplets grew in number and size and began to accumulate proteins with known antimicrobial activity. What’s more, activated lipid droplets became uncoupled from mitochondria, driving a metabolic shift within the cell toward an environment more conducive to host defense.

“In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and the antimicrobial cathelicidin, assemble into complex clusters on lipid droplets (LDs),” the article’s authors wrote. “LPS additionally promotes the physical and functional uncoupling of LDs from mitochondria, reducing fatty acid metabolism while increasing LD-bacterial contacts.”

With antibiotic-resistant superbugs on the rise, researchers are determined to find alternative ways to fight infection. One possibility is ramping up the body’s natural defenses.

“We showed that upon infection of white blood cells called macrophages, lipid droplets move to the part of the macrophage where the bacteria are present,” said Matt Sweet, PhD, another corresponding author and a professor of immunology and microbiology at Queensland.

The bacterial infection also changed the way that white blood cells used energy. “Lipid droplets can be used as a fuel source for mitochondria when there aren’t enough other nutrients,” Sweet added. “During an infection, lipid droplets move away from the mitochondria and attack the bacteria instead, altering metabolism of the cell.”

Parton was inspired to continue this research after the phenomenon was seen in fruit flies. “Most people thought the lipid droplets were ‘blobs of fat,’ only useful for energy storage,” he noted. “But now we are seeing that they act as metabolic switches in the cell, defend against infection and much more—there are now entire scientific conferences of researchers working on them.

“Our next step is to find out how the lipid droplets target the bacteria. By understanding the body’s natural defenses, we can develop new therapies that don’t rely on antibiotics to fight drug-resistant infections.”

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