Antiviral Nonspecific Immunity of Human Placenta at Term: Possible Role of Endogenous Tumor Necrosis Factors and Interferons

Abstract

The antiviral immunity of human placenta and amniotic membrane in an organ culture (OC) system was studied. Freshly isolated explants of most of the placentas at term and the amniotic membranes were found to be relatively resistant to herpes simplex virus type 1 (HSV-1), encephalomyocarditis virus (EMCV), and vesicular stomatitis virus (VSV) infections. After in vitro aging, however, the OC acquired the sensitivity to the viruses. In about 66%-90% of placentas, resistance of freshly isolated explants to the infection was observed. This indicates that the placentas displayed a constitutive immunity against the viruses. To study the role of endogenous cytokines in antiviral immunity, we added specific antibodies neutralizing IFN and TNF activities to VSV-infected OC and checked their influence on viral replication. Increases of 10-fold to 100-fold of VSV replication in the OC treated with anti-TNF-alpha, anti-IFN-alpha, anti-IFN-gamma or anti-IFN-beta sera were observed. The results indicate the importance of the endogenous cytokines in placental and amniotic membrane immunity. However, we did not observe a simple correlation between the spontaneous IFN and TNF production and the level of resistance against viruses. In view of the results, the participation of TNF and IFN in the constitutively expressed immunity of human placenta is of a more complex nature.

A Specific Interferon (IFN)-stimulated Response Element of the Distal HLA-G Promoter Binds IFN-regulatory Factor 1 and Mediates Enhancement of This Nonclassical Class I Gene by IFN-β

“…Alteration of HLA-G or locus-specific class I gene expression may also interfere in the balance between escape from cytotoxic T lymphocytes and maintenance of protection from NK cells (16 -19, 57). Given that IFN-␤ is produced in virally infected trophoblast and amnion (58,59), specific pathways of HLA-G modulation could permit infected cells to block NK and T-cell responses, as seen during maternal-fetal transmission of human cytomegalovirus (60) or human immunodeficiency virus. Alternatively, lysis of infected material could be triggered by CD94/NKG2C receptors through HLA-E surface expression or by HLA-G-restricted T-cell Receptor and thus prevent pathogen spreading from the placental cells to the fetus.…”

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

“…Thus within the context of the broad scope of IFN effects, it seems plausible that pregnancy-associated IFNs may also participate in protection of the fetus against vertically transmitted viruses. Support for such a notion has been provided by experiments with vesicular stomatitis virus (VSV) in vitro [Paradowska et al, 1996] and by a population study of intrauterine herpes simples virus (HSV) infection [Zdravkovic et al, 1997].…”

Resistance of human leukocytes to vesicular stomatitis virus infection as one of the innate antiviral immune activities; participation of cell subpopulations.

“…The resistance of murine macrophages and Kupffer cells to HSV infection has been known much earlier [4][5][6][7]. We found that the resistance is present not only in macrophages, but also in other cells ex vivo, and that is not directed against HSV only, but also against viruses belonging to different taxonomic groups such as encephalomyocarditis virus (EMCV, Picornaviridae), and vesicular stomatitis virus (VSV, Rhabdoviridae) [8][9][10][11]. The resistance of freshly isolated human peripheral blood leukocytes to viral infection was a good reason for elaboration the test for measuring the degree of innate immunity [8].…”

“…Our results showed that kinetics of VSV replication in freshly isolated human peripheral blood leukocytes (PBL) indicates degree of the resistance to viral infection. The lack of VSV replication in the cells (0-1 log TCID50) indicates complete resistance, low level of VSV replication (2-3 log) partial resistance, and high VSV titer (more than 4 log) very low or lack of the resistance [9].…”