How helpful gut microbes send signals that they are friends, not foes

The finding in mice may help explain why a body’s immune system doesn’t kill beneficial bugs


MICROBE MYSTERY  Segmented filamentous bacteria (green) hook into the gut walls (pink) of many animals, including mice, birds and humans. Why the immune system doesn’t attack these bacteria, as well as other beneficial gut microbes, has been a mystery.

I.I. Ivanov and D.R. Littman/Mucosal immunology 2010

Some gut bacteria really put the hooks into their host — but in a good way. Observations in mice show that certain filamentous microbes use a hooklike appendage to send messages that researchers believe are aimed at preventing immune cells from attacking the microbes.

The finding, reported in the March 8 Science, could help explain how an immune system distinguishes friendly gut bacteria from deadly pathogens, says microbiologist Primrose Freestone of the University of Leicester in England, who was not involved in the research.

Because the gut provides an easy gateway for microbes to infect a person or other animal, the intestine is replete with immune cells ready to attack. Researchers have closely examined how immune cells such as T cells recognize and attack pathogens like E. coli. But it’s unclear why these same immune cells don’t kill the trillions of gut microbes that help with digestion and keep people healthy.

Immunologist Ivaylo Ivanov at Columbia University and his colleagues examined segmented filamentous bacteria, a group of gut microbes found in the intestines of many animals including mice, fish and humans. These symbiotic bacteria have a hooklike appendage called a holdfast that attaches them to cells on the gut’s wall.

HOOKED ON Tiny vesicles emerge from the tip and side of a hook used by a bacterium to latch onto the lining of the gut, as seen in this computer reconstruction superimposed onto a microscope image. The bacterium uses these vesicles to carry antigens (small tan dots at center right) for communication with immune cells. M.S. Ladinsky et al/Science 2019

Microscopic 3-D images of holdfasts from more than 200 individual bacteria cells revealed small bubbles, or vesicles, emerging from the hook’s sides and tips and budding off within the intestinal wall.

“This was something nobody had noticed before,” though researchers have studied segmented bacteria since the 1960s, Ivanov says. Chemical tests revealed that the vesicles, like delivery packages, contained the bacteria’s antigens — proteins that immune cells use to recognize a foreign body. Usually, antigens stimulate immune cells to attack and kill an invader. But in this case, although T cells were activated, they didn’t go after the bacteria.

“We’re maybe looking at some new biology,” perhaps a new way of communicating, Ivanov says. “I was not expecting to identify a new type of interaction.”

A T cell’s response may depend on how the antigens are delivered, he suggests. For example, the immune cell may read antigens differently if they are packaged within vesicles released in gut cells rather than exposed on the surface of the invading microbe. “This is just our hypothesis,” Ivanov says.

It’s unknown whether this process is actually suppressing the immune response, and if other gut microbiota might use similar forms of communication. This “is a nice step in terms of understanding the mechanism,” Freestone says, “but there’s still more work to do.”

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