Triggering autoimmune assaults

Mouth bacteria unleash inflammation-inducing protein

SAN DIEGO — Our bodies provide food and shelter for trillions of microbes — bacteria, yeasts and other squatters. Now, researchers report that a few resident species release a substance that can inappropriately rev up the immune system. If this happens at the wrong time, animal tests suggest, the body may launch a dangerous assault against itself.

Once such an autoimmune attack begins, the body finds it hard to shut it down, notes Robert B. Clark. The question has always been what triggers autoimmunity — the condition underlying multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and a host of other disorders.

Clark’s team, at the University of Connecticut Health Center in Farmington, has stumbled onto one new candidate culprit. It’s a fatty compound — phosphoethanolamine dihydroceramide, or PEDHC for short — produced by bacteria residing in the human mouth. The researchers learned about it from a dental colleague, Frank Nichols, who noticed that it caused inflammation in test tube studies and showed up in human tissues that experienced inflammation.

Curious about whether it might affect autoimmunity, Clark’s group tested PEDHC in a mouse model for MS known as experimental autoimmune encephalomyelitis.

To bring on the disease, researchers inject rodents with an emulsion containing brain proteins together with a chemical that enhances immunity. Soon, immune machinery in the mice begins mistaking the brain proteins as alien and attacks them. Immune scouts find plenty more of the “alien” proteins in the rodents’ actual brains, unleashing autoimmune disease there within 12 to 17 days.

The induced autoimmunity develops two to four days earlier and is far more severe in animals that also receive PEDHC, even in trace amounts, the immunologists reported in April in San Diego at the Experimental Biology meeting.

“We all harbor cells that could cause autoimmune disease,” Clark explains, but it develops only when a certain poorly defined cascade of features or events occur, in a particular order.

It’s likely that most people develop conditions that might trigger autoimmunity, he says — but never quite get there. His group’s new data now indicate that exposure to an additional hyperstimulatory agent — like PEDHC — may tip the balance.

Administering PEDHC alone doesn’t turn on autoimmunity, Clark says. It appears to be a problem only when the body has first been primed to attack itself by some as yet poorly understood events. Then the fatty compound can trigger a full-scale assault.

The findings support a burgeoning interest in how resident — or commensal — bacteria affect immunity. Some experts suspect the products of these bugs, such as PEDHC, may constitute formerly unsung but important pieces of the puzzle about what influences autoimmunity on the molecular level.

PEDHC’s oral source, Porphyromonas gingivalis, is not among the body’s nobler squatters. This germ can cause inflammation of tissues in the mouth, though good dental care can keep these bugs from harming gums and teeth.

Because PEDHC is not produced by mammalian cells, the body appears to recognize it as foreign.

Indeed, says William Housley, a member of the Connecticut team, when immune system clarions known as dendritic cells encounter this fatty substance, they appear to “misinterpret it as a bacterial infection, even though there may be no bacteria present.” If this occurs when the body is already primed to attack itself, the immune reaction may go ballistic.

Brushing teeth may be enough to release some of the fatty substance into the bloodstream, Clark says. From there, it can flow to wherever dendritic cells might be primed to attack.

And it’s not just oral bugs that may play such a role. Clark points out that several different bacterial species found in the human gut and vaginal tract also make PEDHC.

The mouse data argue that “a very important trigger that we have been overlooking for years in the development of autoimmune diseases lies within us,” Clark says.

The findings are potentially very important, argues Nicholas LaRocca of the National Multiple Sclerosis Society, which funded the work: “It presents a new area to look at in terms of possible therapeutic agents” to prevent autoimmune diseases or diminish their severity.

 

Janet Raloff

Janet Raloff is the editor of Science News for Students, a daily online magazine for middle school students. She started at Science News in 1977 as the environment and policy writer.

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