Fat cells surrounding the lymph nodes could switch jobs in response to a distant infection, taking on immune cell functions, researchers at Johns Hopkins University reported in the May 3, 2022, online issue of Cell Metabolism.

Co-corresponding author Edward Pearce, a Bloomberg Distinguished Professor at Johns Hopkins University, told BioWorld Science that "the paper adds to an appreciation, which I think is growing, of the importance of adipose tissue for health."

"Conceptually, people think of fat as being bad," he said. "But the reality is that adipose tissue serves a lot of really important functions for healthy living."

Fat cells, or adipocytes, were once seen as more or less passive energy storage vehicles. But they also secrete signaling molecules -- the adipokines -- that affect multiple other tissues.

Many of the adipokines' effects are in the area of metabolism. But there are also clues that adipose tissue has a direct relationship with the immune system.

Some of those clues are functional. The loss of subcutaneous fat that is a feature of aging is associated with an increased susceptibility to skin infections. Other researchers had previously demonstrated that fat cells could secrete antimicrobial peptides in response to skin infections, demonstrating that "fat can really be important in the protection against infection." That importance shows up anatomically, as well.

"All adipose tissue in our body... has a noticeable immune cell component," he said. "In adipose tissue, there are lots of immune cells in between the adipocytes."

The lymph nodes, on the other hand, which like the bone marrow and the spleen are one of the immune system's major base camps, are surrounded by fat tissue.

"That was what we were interested in exploring," Pearce said. "Why have we evolved to have fat around our lymph nodes?"

Especially when it responds to infections, the immune system has to expand and mobilize almost explosively, and Pearce, co-corresponding author Erika Pearce, and their colleagues initially hypothesized that the fat cells were around the lymph nodes as a sort of pantry, to provide the extra energy that is needed to fight an infection.

But "we didn't find any evidence for that," Pearce said.

Mice infected with the intracellular bacteria Listeria monocytogenes or Staphylococcus aureus had a rapid T-cell response and were able to clear the infections, even if the adipose tissue surrounding their lymph nodes was unable to provide immune cells with lipids as fuel. Instead, what the team found was "massive changes related to the adipose tissue taking on a quite different role than it normally had."

Gene expression analyses showed that during infection, there were changes in the expression levels of "a suite of metabolism-, immune- and inflammation-related gene networks. The expression of several genes involved in lipid metabolism (Cd36, Lpl and Adipoq), the canonical function of adipocytes, was downregulated over time after infection, whereas the expression of a host of genes associated with immune function (Cd86, Nos2, Ifngr1, Cd80, Il6, Cd74, H2-Aa, Cd1d1 and Nod1) was induced... These data suggest a marked functional refocusing of adipocytes during infection away from fat metabolism and toward host defense."

On a molecular level, interferon-gamma secreted by innate immune cells led to the production of nitric oxide by the adipocytes, which enabled them to clear the bacteria.

The team concluded that "fat tissue can act as a second layer of defense against infection," Pearce said.