Relationships of CD163 and CD169 positive cell numbers in the endometrium and fetal placenta with type 2 PRRSV RNA concentration in fetal thymus

Abstract

Several routes of porcine reproductive and respiratory virus PRRSV transmission across the porcine diffuse epitheliochorial placentation have been proposed, but none have been proven. The objectives of this study were to investigate associations between numbers of CD163 and CD169 positive macrophages, cathepsin positive areolae, and type 2 PRRSV load at the maternal–fetal interface in order to examine important factors related to transplacental infection. On gestation day 85 ± 1, naïve pregnant gilts were inoculated with PRRSV (n = 114) or were sham inoculated (n = 19). At 21 days post-inoculation (dpi), dams and their litters were humanely euthanized and necropsied. Samples of the maternal–fetal interface (uterus with fully attached placenta) and fetal thymus were collected for analysis by RT-qPCR to quantify PRRSV RNA concentration. The corresponding paraffin-embedded uterine tissue sections were subjected to immunohistochemistry for PRRSV nucleocapsid N protein, CD163, CD169, and cathepsin. Our findings confirm significant increases in the numbers of PRRSV, CD163 and CD169 positive cells at the maternal–fetal interface during type 2 PRRSV infection in pregnant gilts. PRRSV load in fetal thymus was positively related to CD163+ cell count in endometrium and negatively related to CD163+ cell count in placenta, but unrelated to CD169 counts or cathepsin positive areolae. The endometrium:placenta ratio of CD163 cells, and to a lesser extent CD169 cells, was significantly associated with an increase fetal viral load in thymus. These findings suggest a more important role for CD163+ cells following trans-placental PRRSV infection, but dichotomous responses in endometrium and placenta for both CD163 and CD169 cells.

Type 2 porcine reproductive and respiratory syndrome virus infection increases apoptosis at the maternal-fetal interface in late gestation pregnant gilts

“…In the lamina propria of the endometrium, the majority of the cells undergoing apoptosis were inflammatory cells, macrophages and lymphocytes. Since lymphocytes have not been reported as being PRRSV-permissive, and our related study confirmed that low numbers of PRRSV antigen-positive macrophages in the lamina propria [ 19 ], it is possible that significant apoptosis of individual lymphocytes may be the indirect effect of PRRSV replication in the susceptible macrophages [ 21 ] possibly caused by secretion of pro-apoptotic cytokines, e.g. TNFα [ 22 ].…”

“…Briefly, on 85±1 gestation day, 114 PRRSV-naïve pregnant gilts were intramuscularly and intranasally inoculated with PRRSV (10 5 TCID50 total dose, NVSL 97–7895 [ 18 ], GenBank Accession No. AF325691) and 19 negative control pregnant gilts were sham inoculated with minimum essential medium [ 19 ]. At 21 DPI, dams and their litters were humanely euthanized for necropsy examination.…”

“…Immunohistochemistry (IHC) for detection of PRRSV antigen was performed on all 250 tissue sections as previously described [ 19 ] using mouse monoclonal antibody against PRRSV nucleocapsid N protein at dilution 1:200 (SDOW17, Rural Technologies Inc., Brookings, USA).…”

“…Quantitative analyses of TUNEL and PRRSV antigen IHC staining was performed using an Image-Pro Plus, version 7 software (Media Cybernetics, Inc., Rockville, MD, USA) as previously described [ 19 ]. Briefly, ten microscopic fields of the endometrium, captured using a 20X microscope objective lens.…”

Zika Virus Causes Persistent Infection in Porcine Conceptuses and may Impair Health in Offspring

“…The limitation of the porcine model is epitheliochorial placentation, which can confound comprehensive modeling of ZIKV transmission in the hemochorial human placenta. However, all major cell types found in the human fetal placental mesenchyme, like Hofbauer cells, placental fibroblasts, and endothelial cells, are present in the porcine fetal placental mesenchyme ( Karniychuk and Nauwynck, 2009 ; Karniychuk et al, 2011 ; Novakovic et al, 2016 ). The porcine allantochorion performs the same fundamental functions during pregnancy as the human placenta: gas and waste exchange, fetal nutrition and protection.…”