Diverse immune cell profiles in ASFV-associated lymphopenia

Abstract

Pathogenic African swine fever virus (ASFV) remains a lethal causative agent in the domestic pig industry, which poses a burden on the swine market and causes substantial socioeconomic losses worldwide. Currently, there are no commercially efficacious vaccines or specific treatments available for ASF prevention and control. Unfortunately, little is known about the swine immune response upon ASFV infection. Here, we investigated the host immune response discrepancy induced by the field moderately virulent strain ASFV HB-2208 among healthy, diseased and asymptomatic pigs. In the peripheral blood of diseased swine, lymphopenia is caused by the massive loss of bystander lymphocytes, such as γδ T cells, B cells and CD4⁺ T cells. Conversely, ASFV has a strong tropism for the mononuclear phagocyte system (MPS) and partial dendritic cells (DCs), whose antigen-presenting ability is impeded by the downregulation of CD80 and MHC I. However, no significant difference in the number of CD8α^high T cells was detected, whereas the frequencies of NK cells, NKT cells, and regulatory T cells (Tregs) were significantly increased. Additionally, an in vitro model was established with a coculture of primary pulmonary alveolar macrophages (PAMs) and peripheral blood mononuclear cells (PBMCs), which significantly reduced γδ T cells, B cells and CD4⁺ T cells and increased Tregs. The differentiated immune response might aid in enhancing the understanding of ASFV pathogenesis in suids and provide insights into the mechanism of ASFV-induced lymphopenia for further studies.

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Funding

National Natural Sciences Foundation of China(31941005); National Programme on Key Research Project of China(2021YFD1800105-2)