Pig as a biomedical model: Putting the porcine lung dendritic cells/macrophages network into light

Abstract

Introduction Human and mouse respiratory tracts show anatomical and physiological differences, making it necessary to develop alternative experimental models for many respiratory diseases study. Pig has been recognized as a valuable biomedical model, in particular for lung transplantation or pathologies such as cystic fibrosis and influenza infection. However, there is a lack of knowledge about the porcine respiratory system, and more precisely about dendritic cells (DCs) and macrophages (Mθs). Methods Using flow cytometry, confocal microscopy and qRT-PCR, we segregated and studied six populations of pig lung DCs/Mθs: conventional DCs (cDC) 1 and cDC2, inflammatory monocyte-derived DCs (moDCs), monocyte-derived Mθs (moMθs) and interstitial and alveolar Mθs. We then assessed their different functional capacities after cell sorting at steady state in vitro or after an influenza infection in vivo. Results The three DC subsets present migratory and naive T cells stimulation capacities. As observed in human and mice, porcine cDC1 and cDC2 were able to induce Th1 and Th2 responses, respectively. Interestingly, inflammatory cytokines-secreting moDCs increased in the porcine lung upon influenza infection, as observed in the mouse model. Pig cDC2 shared some human characteristics that are not observed in mice, namely the expression of FCɛRIα and Langerin, and an intra-epithelial localization. Conclusions This work, by unraveling the extended similarities of the porcine and human lung DC/Mθ networks, highlights the relevance of pig, both as an exploratory model of DC/Mθ functions and as a model for human inflammatory lung pathologies.