Influenza is a major public health concern worldwide that can cause severe illness or death. Data is still being collecting for the 2024-2025 flu season in the U.S., but during the 2023-24 season there were an estimated 470,000 hospitalizations and 28,000 deaths. In addition to the serious public health concerns for people, influenza can pose a threat to the swine industry, including the potential for swine infections to lead to the emergence of pandemic influenza strains.
Pigs as Influenza Models
Pigs and humans have many similarities in their pulmonary systems, including anatomy, size, and immune responses. These similarities make pigs a useful pre-clinical model for the development of therapeutics and vaccines against human respiratory pathogens.
Given the importance of pigs in influenza A virus (IAV) epidemiology and their potential as pre-clinical models for human IAV infections, it is important to understand the pig anti-IAV response. Despite this, many aspects of the pig immune system remain poorly understood, posing a barrier to improving both human and swine health.
Influenza Immune Responses
To address this, new research in The Journal of Immunology describes key events in the pulmonary anti-IAV response of pigs, opening new avenues for the development of IAV vaccines and therapies, and enabling the improved use of pigs as a model for human IAV infection and immunity.
“Pigs are increasingly used to model human microbial infections and respiratory disorders. The information we uncovered in this study is important to determine where pigs may succeed and fail to predict human pulmonary immune responses,” said Dr. John Driver, Associate Professor in the Division of Animal Sciences at the University of Missouri, who led the study.
Dr. Driver and his team created a cell atlas of infant pig lungs using single-cell RNA sequencing. “The atlas helps understand the porcine anti-influenza defense system, which is important to make progress in the design of more protective IAV vaccines and antiviral therapies,” said Dr. Driver. The team then characterized the single-cell landscape of lung leukocytes of healthy pigs compared to pigs infected with the 2009 pandemic H1N1 IAV with or without the antiviral therapy oseltamivir. They compared the results in pigs to well understood human and mouse models, further informing the suitability of pigs as models for human pulmonary immune responses.
The comparison of different species’ pulmonary responses revealed conserved features and species-specific differences in cell states and cell types during influenza infection. The data demonstrated how IAV infection causes robust antiviral transcriptional responses in multiple lymphoid and myeloid cell types, distinct patterns of cell-cell cross-talk, and how anti-viral therapy oseltamivir altered these responses.
Future Research
“Over the long term the data may be useful for elucidating several important yet poorly understood aspects of pig IAV immunity such as host factors that influence virus transmission and early life imprinting of the influenza virus-specific memory lymphocyte compartment,” said Dr. Driver.
The researchers are building on these findings by performing similar studies in genetically modified pigs that lack different immune cell populations to elucidate the role of these cells in IAV responses.
This paper can be found in The Journal of Immunology (The JI), published by the American Association of Immunologists. As one of the most highly cited journals in the field of immunology, The JI is committed to describing novel findings in all areas of experimental immunology, including basic and clinical studies.
