A new collaborative study with the Pirbright Institute on the porcine respiratory system, has shown that pigs are a valuable intermediate model between mice and humans for studying influenza, and other respiratory diseases affecting humans.
The pig immune system presents many similarities to those of humans and, unlike mice, pigs are a natural host for the Influenza A Virus (IAV) and exhibit the same symptoms. There has been a lack of knowledge about the porcine respiratory immune system however. For example, previous studies that described pig lung immune cells, did not enter in dendritic cells (DC) and macrophage (M) subpopulation details.
The DC/M network is one of the main components of the respiratory immune system, and is involved in sensing foreign antigens, controlling inflammation and initiating the immune response.
In this study, which was a collaboration between Dr Maria Montoya from The Pirbright Institute and research teams from France and Spain, scientists were able to specifically define for first the time the phenotypes and functions of the DC/M populations in the different compartments of the pig respiratory tract, at a steady state (non infected) and upon IAV infection.
Researchers segregated and studied six populations of pig lung DC/M cells and assigned six respiratory DC/M cell types to their mouse and human counterparts.
The immune cells were identified and sorted in a steady state by identifying their receptors and the quantity in which they were expressed in the cells, as well as looking at their morphology and gene expression. Key behaviours of the cells were also examined, such as their ability to migrate to lymph nodes (areas where immune cells can sample foreign substances), ability to activate other immune cells and ability to produce molecules that aid immune response.
Scientists also examined how the populations of these cells varied between different locations within the respiratory system. All of these factors helped to characterise the equivalent immune cells in human and mice models for comparison.
Once the cell types were characterised, their interactions were tested upon Influenza infection to determine how the immune cells responded. Comparisons were then made against the responses of the equivalent cells in humans when infected with the same strains.
Results showed that although there were some differences between the pig respiratory immune cells and human cells, the pig model shows a greater resemblance to the human model than that of the mouse model.
Dr Montoya said: “This study aimed to gain better understanding of the pig respiratory immune system. By unravelling the extended similarities of the porcine and human lung DC/M networks, we have been able to show that pigs are a pertinent and intermediate model between mice and humans in the study of human inflammatory lung pathologies”.