Is it the immune system or is it the lymph nodes?

Or is it both?

That’s the question now surrounding a debate over the possible causes of chronic diseases such as sarcoidosis and rheumatoid arthritis.

The answer may point to the root cause of these debilitating ailments and dictate possible treatments down the line.

In a perspective published in the journal Science, Dr. Carl Nathan, chair of the department of microbiology and immunology at Weill Cornell Medical College, suggests that immunologic scarring left behind by infections could account for a wide range of these diseases.

Bacteria such as lactobacilli may be left behind in the lymph nodes after an infection clears up, leaving a “scar” that could contribute to chronic immune dysfunction, Nathan argued.

Lactobacilli are often considered a friendly bacteria. A healthy human body houses lactobacilli in its gut.  But when those microbes go on walkabout, they might become alien invaders.

“We’re not talking about in the gut. We’re talking about the lymph nodes,” Nathan told Healthline. “I think it’s worth considering.”

The Debate Over Disease

Nathan’s column was a response to a study led by D.M. da Fonseca that concluded that a previous infection can set the stage for chronic inflammation by impairing the immune system’s checks and balances.

In their research, da Fonseca and his team infected the intestines of mice with bacteria. After the initial infection cleared, the researchers noticed long-lasting changes to the immune systems of the mice. They concluded that this could lead to chronic ailments.

Nathan’s theory is little different.

Nathan said the presence of lactobacilli in lymph nodes indicates the normally helpful gut bacteria may develop qualities to evade or suppress the immune system. 

In these cases, the gut wall could have gaps in it to allow the bacteria to migrate to other parts of the body.

“To actually find live bacteria in the lymph nodes for a long period of time is abnormal,” Nathan said.

Why the Debate Matters

The lymphatic and immune systems work together to defend against disease and infection. In autoimmune diseases, the immune system attacks healthy tissues, causing chronic inflammation. Figuring out where the signals begin to get crossed and how, is the holy grail of this type of research and the key to treatments or cures.

“There are many major inflammatory disorders that look like they could be triggered by infection, but one has to be able to find the infectious cause,” Nathan said. “Periodically in the history of medicine the source of the infection has been found.”

Christine McDonald, Ph.D., an associate staff member at the Lerner Research Institute at the Cleveland Clinic, agrees.

She said it seems apparent that bacteria play at least a role in the “vicious cycle of inflammation” in autoimmune diseases.

She said the two studies could point the way for scientists to narrow down how those bacteria thrive and where they reside. It could involve either the immune system or the lymph nodes or even a combination of the two.

“It’s a great step forward, but there are still a lot of questions,” McDonald told Healthline. “It’s a little bit of chicken and egg.”

Once some of the mysteries are unlocked, scientists can start looking at ways to prevent these diseases from spiraling out of control.

“It provides us with a new opportunity to investigate treatments,” she said.