BioEd Online

Helpful bacteria don't just aid digestion; they also fend off the flu, according to a report published today in the Proceedings of the National Academy of Sciences¹.

A research team led by Akiko Iwasaki, an immunologist at Yale University in New Haven, Connecticut, found that mice treated with neomycin antibiotics were more susceptible than control mice to influenza viruses. It turned out that neomycin-sensitive bacteria naturally present in the mice's bodies provided a trigger that led to the production of T cells and antibodies that could fight an influenza infection in the lungs.

The bacteria kick-started the flu-fighting pathway by activating 'inflammasome' protein complexes in the immune system. The inflammasomes then pushed precursors of an immune protein — the cytokine interleukin 1-ß — into a chemically mature state. Mature interleukin 1-ß triggered dendritic immune cells to migrate to lymph nodes in the lungs, where they initiate a potent attack on influenza viruses. When antibiotics eliminated the bacteria, inflammasomes failed to launch and the virus multiplied.

"This is a landmark paper that opens up new avenues of research and suggests new possibilities for ways to treat and prevent viral infections," says Sarkis Mazmanian, a microbiologist at the California Institute of Technology in Pasadena.

Gut feeling

Microbiologists have known that microbes inhabiting mammals interact with the immune system since the 1950s, when they found that eliminating bacteria in newborn mice prevented them from developing a normal immune system².

In the past decade, research has focused on how bacteria regulate immune pathways relevant to the health of the host's gut, where the bulk of the body's roughly 100 trillion 'commensal' — harmless or beneficial — bacteria reside. For example, an imbalance in the proportions of certain harmful and beneficial gut bacteria seems to over-activate inflammation-inducing cells, possibly fuelling inflammatory bowel disease³.

A handful of detailed reports in the past five years have hinted that helpful microbial interactions don't stop at the gut⁴, but Iwasaki's study is the first to pinpoint how bacteria combat infections in the lungs.

"This study contributes to a growing body of literature showing that signals from commensal bacteria can have an impact on immune cells in multiple tissues," says David Artis, an immunologist at the University of Pennsylvania in Philadelphia. "If certain antibiotics have an effect on our ability to mount a response against a viral infection, it means that people should be careful to only take antibiotics when they are absolutely needed — particularly in the flu season."

In addition, says Artis, the findings "suggest that our diet might affect our ability to fight viruses by influencing the composition of our commensal bacteria".

But Iwasaki cautions that "we don't yet know enough about which bacteria trigger what pathways to make health recommendations". Her team has not identified the bacteria responsible for the immune response, but Iwasaki suspects that effect is caused by Lactobacillus species residing in the gut. After antibiotics, the populations of these bacteria were significantly diminished in the mice's guts but not in their nasal cavities.

Mazmanian says, "the question is, do bacteria intentionally induce this process in order to protect their hosts from flu infections? Or is the inflammasome non-specifically activated by the bacteria, and one consequence of inflammasome activation just happens to be flu control?"

Either way, "it's become clear that our immune system has evolved to act like an interface for microorganisms to send signals to our body".