Long-Lived Monocyte-Derived Cells Found to Support Lasting Lung Immunity Against Influenza

Influenza remains a persistent public health burden in the United States, with the CDC estimating 51 million illnesses, 710,000 hospitalizations, and 45,000 deaths during the 2024-2025 season alone. Vaccination remains the most effective preventive tool, but current injectable vaccines do not reliably stop the virus from establishing infection in the respiratory tract, leaving a persistent gap between vaccination and true mucosal protection.^1,2

A newly published study in Nature Immunology identifies a previously unrecognized population of long-lived monocyte-derived cells in the lung that may help close that gap, offering a new cellular target for next-generation nasal vaccine design.^1-3

A Monocyte Population That Does Not Disappear

Investigators at the University of Rochester Medical Center set out to understand how the immune system builds and sustains tissue-resident memory CD8+ T cells (TRM cells)—specialized immune sentinels that station themselves at the site of viral entry and mount an immediate response upon reinfection.^2,3

Using a mouse model of influenza infection, the research team traced a subset of CCR2-positive monocytes recruited to the lung during acute infection. Rather than dying off after the infection resolved (as monocytes are traditionally thought to do), a fraction of these cells differentiated into a distinct memory-stage population that persisted in lung tissue for more than 4 months.^2,3

Minsoo Kim, PhD, professor of microbiology and immunology at the University of Rochester and the study’s senior author, said the finding challenges long-standing assumptions about which immune cells sustain long-term protection.²

“Our work identified a long-lived monocyte-derived population in the lung that provides essential support for durable T cell immunity,” Kim said in a news release. “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.”²

Galectin-1 Emerges as a Communication Signal

When the investigators selectively depleted these memory-stage monocyte-derived cells, the formation of lung CD8+ TRM cells dropped significantly, and protection against a mismatched, or heterosubtypic, influenza strain was compromised. Further analysis showed that the persisting cells physically colocalized with TRM cells and secreted galectin-1, a protein that directly activated CD8+ T cells and enhanced their sensitivity to transforming growth factor-β, a cytokine known to support tissue residency.³

According to Kim, this signaling relationship points to a specific, targetable mechanism behind TRM maintenance. “We identified galectin-1 as a powerful immune signal that can be used as a vaccine adjuvant to enhance mucosal immunity. This is a completely new approach for improving how vaccines work in the respiratory tract.”²

An accompanying commentary published alongside the study characterized the newly identified cells as inflammatory monocytes that differentiate into persistent, lung-resident galectin-1–positive myeloid cells supporting the long-term maintenance and recall function of influenza-induced TRM cells, reinforcing the significance of the monocyte-T cell relationship uncovered in the work.⁴

Implications for Nasal Vaccine Design

To test whether this pathway could be therapeutically harnessed, the researchers administered recombinant galectin-1 intranasally alongside an experimental live-attenuated influenza vaccine. Mice receiving the galectin-1–adjuvanted vaccine developed significantly stronger memory CD8+ T cell responses in the lung compared with the vaccine alone. Because existing nasal vaccines have historically struggled to generate consistent and durable mucosal immunity, this adjuvant approach represents a potential strategy for improving on current intranasal formulations.^2,3

“Existing nasal vaccines often fail to generate strong or durable protection,” Kim said. “This tells us we need new strategies that can better activate immune memory in the airways.”²

Looking Ahead

The study authors noted that while the findings are promising, they were generated exclusively in animal models, and further work—including the development of more stable galectin-1 formulations—will be needed before any translation toward human vaccines. The implications may extend beyond influenza, as the same principle of reprogramming innate immune cells to support TRM maintenance could inform vaccine strategies against other respiratory pathogens, including those responsible for future pandemics.²

For pharmacists and other health care professionals who are involved in immunization counseling, the study emphasizes that the next wave of respiratory vaccine innovation may look different from current intramuscular formulations, with mucosal delivery and innate-adaptive immune crosstalk playing a central role in vaccine design going forward.

REFERENCES

1. 2024–2025 Influenza Season Summary: Severity, Disease Burden, and Burden Prevented. News release. CDC. March 12, 2026. Accessed September 4, 2026. https://www.cdc.gov/flu-burden/php/data-vis-vac/2024-2025-prevented.html

2. Hidden immune cells in the lung could lead to better flu vaccines. News release. EurekAlert! August 31, 2026. Accessed September 4, 2026. https://www.eurekalert.org/news-releases/1141821

3. Lim K, Dahal A, Lv X, et al. Monocyte-derived galectin-1hi cells provide innate immune help in the generation of functional memory CD8+ T cells. Nat Immunol. (2026) August doi:10.1038/s41590-026-02638-9

4. Heidarian M, Badovinac VP. Good neighbors make lasting memory. Nat Immunol. (2026). 2026 Aug 31. doi: 10.1038/s41590-026-02645-w