Yale Graduate School of Arts and Sciences

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Intestinal Bacteria Found to Protect Lungs from Infection

Graduate student Iris Pang (Immunobiology), working with former postdoctoral fellow Takeshi Ichinohe in Professor Akiko Iwasaki’s lab, has shown that helpful or, at worst, harmless “commensal” bacteria in the intestines actually play an important role in fighting flu infection in the lungs.

Her recent publication about this ground-breaking research in Proceedings of the National Academy of Sciences has attracted much attention in the scientific world and led to the publication of articles in American Scientist , Nature, and Scientific American.

Iris’ study is the first to demonstrate that commensal bacteria provide a signal to the body that prepares other organs, in this case the lungs, to mount an immune response against viruses. Antibiotics, which suppress bacteria in the gut, seem to impair the body's ability to send those signals. The specific mechanism by which the microbes help mount an immune response is still unclear, but Iris and her colleagues suspect it might involve cytokines, cell-signaling protein molecules known to activate immune cells.

illustration commensal flu

Proposed mechanism by which the gut microbiota support respiratory immunity against influenza virus infection. Inflammasome activation and IL-1beta release are required for protective adaptive immune defense against influenza virus infection. Professor Iwasaki and her group speculate that the gut-resident microbiota provide signals to the lung via systemic circulation. In the respiratory tract, commensal-derived signals induce transcriptional and translational activation of pro-IL-1beta. Influenza virus infection triggers the formation of the inflammasome and the processing of pro-IL-1beta into mature IL-1beta for release into extracellular space. Inflammasome-dependent IL-1beta released in the lung regulates the development of virus-specific CD8 T cells important for efficient clearance of the virus.

Iris became interested in studying influenza viruses while doing her rotation in Iwasaki's lab, which focuses on many aspects of immunity and infection, including how the body recognizes viruses and how that information is used to generate protective adaptive immunity.

“Our ultimate goal is to utilize the knowledge we gain through these areas of research in the rational design of effective vaccines or microbicides for the prevention or transmission of viral and bacterial pathogens,” says Iwasaki.

“During my rotation, I was fascinated by an earlier study from this lab on the role of inflammasomes – cytoplasmic protein complexes that sense damage and stress signals in the cells – in viral detection and induction of protective adaptive immune responses to flu. Many stimuli can trigger the formation of the inflammasomes, including a number of bacterial products. Knowing that mammals live with a lot of commensal bacteria in their gut, we started to wonder whether the gut bacteria would have any role in regulating inflammasome-dependent responses and shaping immunity to influenza viruses,” Iris explains.

After her rotation was over, she joined the lab and worked side by side with Ichinohe, who had pioneered multiple projects on influenza virus. They used a mouse model of respiratory influenza, giving mice a combination of antibiotics in their drinking water to deplete the bacterial composition in the gut and then infecting the mice with the flu virus. The animals exhibited a significantly impaired immune response compared to the control group. The bacteria-deficient mice had reduced levels of T-cells and influenza-specific antibodies, which play a key role in fighting infection. As a result, the animals had high amounts of virus in the lungs. Together with Ichinohe, they uncovered an unexpected role of the commensal bacteria's contribution to host sensing of viral-inflicted damage and adaptive immunity to flu.

This project is part of Iris’s dissertation, which focuses on how sensing of flu viruses by the host triggers the formation of protective adaptive immunity. Collaborating with another graduate student in the lab, Padmini Pillai, Iris hopes to extend their current findings by using mice that are born without these germs. Currently, Iris is also looking at the contribution of other viral recognition pathways to antiviral defense during flu infections.

Iris came to Yale after earning her undergraduate degree from the University of Washington in Seattle, where she conducted research in immunology under Professor Alexander Rudensky. She chose Yale “because of the exceptional immunobiology program here,” and reports that she “likes everything” about her lab, noting specifically that “my PI is supportive, and my colleagues are hardworking, respectful, collaborative, and fun to work with.”

Yale will always be special to her because it is here that she met her husband, Kevin Yip (PhD ’09, Computer Science). They were married last year in Hong Kong. He now works as an assistant professor in Hong Kong, where his family resides. They travel back and forth when they can. Iris plans to move to Hong Kong following her graduation.

Iris Pang