Current status of monocyte differentiation-inducing (MDI) factors derived from human fetal membrane chorion cells undergoing apoptosis after influenza virus infection

Abstract

Influenza virus infection induces apoptosis and the expression of a set of pro-inflammatory cytokine genes, such as interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-beta and IFN-gamma, in cultured human fetal membrane chorion cells. Monocyte differentiation-inducing (MDI) activity in culture supernatants is simultaneously increased by the virus infection. The MDI activity is predominantly influenced by IL-6 molecule in culture supernatants, and partly by TNF-alpha and IFN-beta, but not IFN-gamma, molecules. The MDI factors are able to induce the mRNA expression of macrophage class A scavenger receptor (SR-A), which is one of adhesion and apoptotic cell-recognizing molecules, and gp91(phox), which is a catalytic subunit of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme complex, on monocytic cells. As a result, monocytes are initiated to differentiate into well-matured macrophages capable of adhering and producing superoxide through NADPH oxidase. The matured macrophages, obtained from human monocytic leukemia THP-1 cells by the treatment with MDI factors, phagocytose apoptotic chorion cell debris resulting from the virus infection. Subsequent to phagocytosis, an abrupt increase of superoxide production by macrophages may occur. In this article, we summarize recent knowledge about the MDI factors derived from human fetal membrane chorion cells undergoing apoptosis after influenza virus infection, and discuss their possible pathological roles during pregnancy.

Keywords: Fetal membranes; apoptosis; cytokines; influenza virus; macrophages; phagocytosis.

Figure 1. A possible tissue injury model of fetal membranes during intrauterine influenza virus infection

MDI factors containing IL-6, TNF-α and IFN-β are secreted from chorion cells in response to the synthesis of influenza virus macromolecules prior to apoptotic cell death. The MDI factors bind to their receptors on maternal monocytes in the decidua tissue, resulting in the expression of SR-A and gp91^phox genes. The matured macrophages phagocytose apoptotic chorion cell debris resulting from the virus infection. It is possible that an abrupt increase in superoxide production by phagocyte NADPH oxidase occurs during phagocytosis, and superoxide induces apoptosis in non-infected chorion cells. MDI factors-relating these pathways represent part of mechanisms of pregnancy-associated complications during intrauterine influenza virus infection.