Human and mouse respiratory tracts show anatomical and physiological differences, which will benefit from alternative experimental models for studying many respiratory diseases. 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 immune system. Here we segregated and studied six populations of pig lung dendritic cells (DCs)/macrophages (Mθs) as follows: conventional DCs (cDC) 1 and cDC2, inflammatory monocyte-derived DCs (moDCs), monocyte-derived Mθs, and interstitial and alveolar Mθs. The three DC subsets present migratory and naive T-cell stimulation capacities. As observed in human and mice, porcine cDC1 and cDC2 were able to induce T-helper (Th)1 and Th2 responses, respectively. Interestingly, porcine moDCs increased in the lung upon influenza infection, as observed in the mouse model. Pig cDC2 shared some characteristics observed in human but not in mice, such as the expression of FCɛRIα and Langerin, and an intra-epithelial localization. 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.

Monocytes-macrophages, the target cells of African swine fever virus (ASFV) are highly heterogeneous in phenotype and function. In this study, we have investigated the correlation between the phenotype of specific populations of porcine macrophages and their permissiveness to ASFV infection. Bone marrow cells and fresh blood monocytes were less susceptible to in vitro infection by ASFV than more mature cells, such as alveolar macrophages. FACS analyses of monocytes using a panel of mAbs specific for porcine monocyte/macrophages showed that infected cells had a more mature phenotype, expressing higher levels of several macrophage specific markers and SLA II antigens. Maturation of monocytes led to an increase in the percentage of infected cells, which correlated with an enhanced expression of CD163. Separation of CD163+ and CD163- monocytes demonstrated the specific sensitivity of the CD163+ subset to ASFV infection. In vivo experiments also showed a close correlation between CD163 expression and virus infection. Finally, mAb 2A10 and, in a lower extent, mAb 4E9 were able to inhibit, in a dose-dependent manner, both ASFV infection and viral particle binding to alveolar macrophages. Altogether, these results strongly suggest a role of CD163 in the process of infection of porcine monocytes/macrophages by ASFV.

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Summary Swine monocytes constitute a heterogeneous population of cells which can be divided into four subsets based on the expression of SWC3, CD14, CD163 and swine leucocyte antigen (SLA) DR markers. These subsets appear to represent different maturation stages in a pathway along which these cells up‐regulate the expression of SLA DR and CD163 antigens and reduce that of CD14. Differences in the expression of adhesion and costimulatory molecules are also patent, with a progressive increase in the expression of CD11a, wCD11R1, CD29, CD49d, CD61, CD1a and CD80/86, and a concomitant decrease in that of wCD11R2. Besides, these subsets differ in their capacity for tumour necrosis factor‐α (TNF‐α) production in response to lipopolysaccharide + interferon‐γ. The CD163+ CD14− SLA DR+ subset produces higher amounts of TNF‐α than the CD163− CD14+ SLA DR− subset, whereas CD163+ CD14+ SLA DR+ and CD163− CD14+ SLA DR+ subsets show intermediate values. CD163+ monocytes also display a higher ability to present soluble antigens to T cells than CD163− monocytes.

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