Breaking the rules: flagellin vs rotavirus

Flagellin is a bacterial protein that activates the innate immune system. Its name comes from flagella, the whips many bacteria use to propel themselves.

On Thursday, a team of researchers led by immunologist Andrew Gewirtz reported in Science that treatment with flagellin can prevent or cure rotavirus infection in animals. Rotavirus infection is one of the most common causes of severe diarrhea and is a major cause of death for children in developing countries.

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Andrew Gewirtz, PhD

Gewirtz’s lab is now at Georgia State, but he and his colleagues initiated this research while at Emory and several co-authors are affliliated with Emory, including immunologist Ifor Williams.

These findings are remarkable for several reasons. One is: give the immune system something from bacteria, and it’s better at fighting a virus? As Gewirtz says in a GSU news release: “It’s analogous to equipping an NFL defense with baseball bats. Blatant violation of all the rules but yet, at least in this case, very effective.”

For me, what was most surprising about this paper was that treatment with flagellin, or immune signaling proteins activated by flagellin, can get mice with severely impaired immune systems – no T cells or B cells at all — to evict rotavirus. These are mice that have to be reared under special conditions because they are vulnerable to other infections. Interferons, well-known antiviral signaling molecules, are also not involved in resisting or evicting rotavirus infection, the researchers found.

That means flagellin must be acting through other immune cells and pathways. One of the types of cells needed is new enough to immunologists that a 2013 overview in Nature Reviews Immunology is titled “Innate lymphoid cells – how did we miss them?”

Indirectly, flagellin appears to stimulate intestinal epithelial cells to become more virus-resistant, the researchers found. Gewirtz says his team is investigating whether treatment with flagellin (or IL-18 and IL-22, the molecules it is acting through) may be helpful in fighting other viral infections such as norovirus.

Although vaccines against rotavirus are available, they have been less effective in developing countries. A NIH virologist quoted in Science says Gewirtz’s findings may explain why: children in developing countries may have been exposed to more flagellin and their cells might destroy live-virus vaccines before they can fully stimulate immunity. Genetics and viral strain mismatch may also affect the vaccines’ efficacy, recent research suggests.

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Posted on by Quinn Eastman in Immunology Leave a comment

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Quinn Eastman

Science Writer, Research Communications qeastma@emory.edu 404-727-7829 Office

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