University of Rochester Medical Center researchers have identified long-lived immune cells in the lungs that may help scientists design more effective nasal vaccines against influenza and other respiratory viruses.
The study, published in Nature Immunology, found that a subset of monocytes can remain in the lungs for months after a flu infection and support tissue-resident memory T cells, which respond where respiratory viruses first enter the body. Researchers also identified the protein galectin-1 as a possible vaccine additive after it strengthened lung immune responses in mice.
The findings challenge the traditional view that lasting immune memory is driven only by T cells and B cells. Monocytes are generally considered short-lived members of the innate immune system, but the study found that some monocyte-derived cells persist in the lungs and help memory T cells survive and function.
“Our work identified a long-lived monocyte-derived population in the lung that provides essential support for durable T cell immunity,” said Minsoo Kim, a professor of microbiology and immunology at URMC and the study's lead author. “This challenges the traditional view that immune memory is driven only by T and B cells, and shows that innate immune cells also play a lasting role.”
How the lung builds immune memory
After an infection or vaccination, the immune system forms memory cells that can respond quickly when the same virus returns. Tissue-resident memory T cells remain in the lungs and other tissues, allowing them to react at the site of infection instead of waiting for immune cells circulating elsewhere in the body.
Kim said those cells are positioned where respiratory infections begin, allowing them to react immediately and limit viral spread. Building that kind of fast, local protection is a central goal of next-generation vaccine development, he said.
Most current flu vaccines are injected into muscle. They are effective at preventing severe illness but do not consistently create strong immune memory in the airways or stop a virus from taking hold in the nose and lungs.
Nasal vaccines are intended to target immunity at that point of entry, but their effectiveness has been inconsistent. The researchers said the newly identified immune-cell interaction could offer another way to strengthen and extend that protection.
Galectin-1 strengthened response in mice
The study found that the persistent monocyte-derived cells produce galectin-1, a protein that helps activate and sustain tissue-resident memory T cells.
When researchers added galectin-1 to an experimental nasal flu vaccine in mice, the immune response in the lungs became significantly stronger. Vaccine additives, also called adjuvants, are used to improve the body's immune response to a vaccine.
Kim called galectin-1 a powerful immune signal that could be used to enhance mucosal immunity, the immune protection found in areas such as the nose and respiratory tract.
The work remains at the animal-study stage, and additional research will be needed before galectin-1 could be considered for use in people. The team is now working to develop more stable forms of the protein that could be safely used as a vaccine additive.
Potential reach beyond influenza
The findings could have implications for vaccines against other respiratory viruses, including viruses associated with seasonal illnesses and pandemics. Researchers said future vaccine designs may be able to improve protection by influencing the long-term behavior of immune cells that live in the lungs, rather than focusing only on antibodies or circulating immune cells.
That could help vaccines stop infection earlier at the point of entry in addition to reducing severe disease. Influenza causes more than 35,000 deaths annually in the United States, according to the URMC release, with children, older adults, pregnant people, those with weakened immune systems and people with chronic conditions among the most vulnerable.
The study's co-authors include Kihong Lim, Ankit Dahal, Xiurui Lv, Herman Li and Laurie Steiner of URMC, along with Mi-Ra Choi and Kyun-Do Kim of the Korea Research Institute of Chemical Technology.
The research was funded by URMC, the National Institute of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute, the National Research Foundation of Korea and the Korea Research Institute of Chemical Technology.
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