Interferon Production by Cultured Human Trophoblasts and Choriocarcinoma Cell Lines Induced by Sendai Virus

Abstract

Human term-placental trophoblasts in primary culture were studied for an interferon (IFN) response when challenged with Sendai virus and compared to three choriocarcinoma cell lines, placental fibroblasts and placental macrophages. Normal trophoblasts were high producers and released both IFN-u and IFN-fl. In contrast, one choriocarcinoma cell line was a low producer and all malignant lines produced only IFN-fl. Circulating monocytes produce IFN-~ but placental macrophages secreted IFN-fl and some IFN-~, suggesting that IFN production may be dependent on the stage of differentiation. A role for trophoblast IFNs in protection of the foetus against virus infections is proposed.In pregnancy, interferons (IFN) may accomplish a number of complex actions at the cellular level, not only in the immunological relationship between mother and foetus but also in the defence mechanism against intrauterine infection of the foetus. Indirect evidence for IFN production by the human placenta was first shown by perfusion studies (Bocci et aL, 1985) in which perfused human placentas at term released IFN in small amounts. In a previous study (T6th et al., 1990), we reported the production of IFN by different cells of the human placenta after stimulation with polyriboinosinic-polyribocytidylic acid [poly(rI)-poly(rC)]. The ability of these cells to produce IFN in response to viruses has not been determined. This may have great importance, especially in the case of trophoblasts, because the foetal component of the maternal-foetal interface during pregnancy is composed of trophoblast cells. This paper describes the IFN response, in primary cell cultures derived from human term placentas and in three different malignant trophoblast cell lines, to Sendai virus, a virus known to be a good IFN inducer in human cells (Lee, 1969).Term placentas from normal pregnancies (36 to 42 weeks gestation) were obtained within 15min of spontaneous vaginal delivery. Trophoblasts were separated essentially as described by Douglas & King (1989), whereas placental macrophages and fibroblasts were separated by the method of Wilson et al. (1983). The purity of the cell populations was tested by indirect immunofluorescence (T6th et al., 1990). Cytotrophoblast cultures used for IFN induction were found to be 98% to 100 % pure. The purity of the fibroblast and macrophage cultures was greater than 95%. The human choriocarcinoma cell lines JAR, JEG-3 and BeWo were from the American Type Culture Collection. Sendai virus, Cantell strain, was grown on 10-day-old embryonated eggs and vesicular stomatitis virus (VSV), Indiana strain, was propagated on monolayers of L929 cells.For IFN production, cells were seeded at 106 per well in tissue culture plates and cultured in 2 ml RPMI-1640 plus 10% foetal calf serum (FCS). After 24 h the medium was removed and 200 haemagglutination (HA) units of Sendai virus in serum-free RPMI were added. Control cultures were incubated with the appropriate dilution of sterile allantoic fluid or with medium alone. After 1 h of adsorption, t...

Viral ssRNA Induces First Trimester Trophoblast Apoptosis through an Inflammatory Mechanism

“…Studies from our laboratory, as well as others, have previously shown that viral products and viral infections trigger the trophoblast to produce type I interferons. 26,48,49 While we found that viral ssRNA triggered a strong inflammatory response in the trophoblast, in parallel to this, viral ssRNA-triggered trophoblast cell death and apoptosis. This involved activation of the caspase pathway, activation of the pro-apoptotic proteins, Bid and Bax, which act on the mitochondria; and inactivation of the inhibitor of apoptosis, XIAP.…”

“…Our observation that viral ssRNA also induces a strong IFN® response in the trophoblast is in keeping with the ability of the placenta to generate a specific anti-viral response. Studies from our lab, as well as others, have previously shown that viral products and viral infections trigger the trophoblast to produce type I interferons 26,48,49.…”

Lack of protection against vertical transmission of HIV-1 by interferons produced during pregnancy in a cohort from East African Republic of Malawi

“…Since the limited permissiveness of the placental tissue for VSV, HSV-1, and encephalomyocarditis virus has been found associated with constitutively expressed IFNs [Paradowska et al, 1996]; also, the trophoblast-derived IFN-␣ and -␤ have been shown effective against VSV in tissue culture [Toth et al, 1990], it appears that placental IFNs might be important for The extent of placental inflammatory changes was expressed on an arbitrary scale from 0 to +3. antiviral immunity in a manner similar to that of classical IFNs.…”

Antiviral activity of bovine uterus and placenta induced by Newcastle disease virus

“…In the human placenta it had been demonstrated that IFN-β was predominantly produced when stimulated by Sendai virus (Toth et al, 1990a) and double-stranded polyribonucleotide (Toth et al, 1990b). In addition, following viral stimulation first trimester human placenta produced higher levels as compared to term cultures (Aboagye-Mathiesen et al, 1993).…”