Monocytes Help Sustain Long-Term Flu Immunity

Influenza causes more than 35,000 deaths annually in the United States, with children, older adults, pregnant individuals, people with weakened immune systems, and those with chronic conditions such as heart disease, metabolic disorders, and cancer at greatest risk. Vaccination remains the most effective prevention tool, but current vaccines do not always stop the virus from establishing itself in the respiratory tract.

New research published in Nature Immunology points to a previously overlooked group of lung immune cells that may help close that gap. In the lungs, tissue-resident memory T cells serve as a first line of defense where infection begins. Minsoo Kim, the study’s lead author, said these cells “are positioned right where infection begins, so they can react immediately and help limit viral spread,” calling them “a central goal for next-generation vaccine design.” Most current flu vaccines, especially injected ones, don’t reliably build strong memory in the airways.

The study found that a subset of monocytes, cells normally considered short-lived, can persist in the lungs for months after influenza infection, helping memory T cells survive and function there. “Our work identified a long-lived monocyte-derived population in the lung that provides essential support for durable T cell immunity,” Kim said, adding that this challenges the view that immune memory depends only on T and B cells.

These monocyte-derived cells produce a protein called galectin-1, which activates and sustains tissue-resident memory T cells. Adding galectin-1 to an experimental nasal flu vaccine in mice significantly strengthened the lung immune response. Kim described galectin-1 as “a powerful immune signal that can be used as a vaccine adjuvant to enhance mucosal immunity,” calling it “a completely new approach for improving how vaccines work in the respiratory tract.”

Existing nasal vaccines, Kim noted, “often fail to generate strong or durable protection,” pointing to a need for strategies that better activate airway immune memory. The findings may extend beyond influenza to other respiratory viruses. As Kim put it, “innate immune cells are not just first responders—they can also shape long-term immune memory,” raising the possibility of vaccines designed to reprogram these cells.

The results so far come from animal models, and researchers are now developing more stable forms of galectin-1 for potential use as a vaccine additive. If the findings hold up in humans, vaccine design could shift toward targeting the long-term behavior of immune cells that reside in the lungs.