Phagocytosis as a potential mechanism for microbial defense of mouse placental trophoblast cells

Abstract

Trophoblast giant cells are active phagocytes during implantation and post-implantation. Phagocytosis decreases during placental maturation as the phagocytic function of nutrition is gradually replaced by the direct uptake of nutrients by the labyrinth zone trophoblast. We hypothesize that, after placental maturation, trophoblast cells maintain phagocytic functions for purposes other than nutrition. This study employs histological techniques to examine the ability of trophoblast cells to phagocytose microorganisms (yeast or bacteria) -in vivo in females receiving thioglycolate to activate macrophages and in vitro in the presence of phagocytic promoters such as interferon-g and complement component C3. Placental trophoblast cells from the second half of gestation show basal phagocytosis that can be dramatically up-regulated by these promoters when microorganisms are inoculated into pregnant animals or introduced into culture systems. Stimulated trophoblast cells phagocytosed organisms more rapidly and in greater numbers than non-stimulated trophoblast exposed to the same numbers of organisms. Taken together, our results indicate that trophoblast cells do not lose their ability to phagocytose during the placentation process, which may imply that trophoblast cells participate in embryonic and fetal innate immune defense through elimination of microorganisms present at the maternal-fetal interface.

Trophoblast phagocytic program: roles in different placental systems

“…A number of recent studies examined the mice trophoblast phagocytosis in vivo and in vitro leading to similar results (Schlesinger and Koren, 1967;Delgado and Santos-Buch, 1978;Pavia, 1983;Drake and Rodger, 1987;Albieri et al, 2001;Amarante-Paffaro et al, 2004;Neres et al, 2008). Fetal transmission of Trypanosoma cruzi experimentally infected in pregnant females depended on pathogenicity of the strain and trophoblast phagocytosis.…”

“…In addition, phagocytosis of zymosan particles administered in pregnant female on day 13.5 of gestation can be seen at placental trophoblast giant cells for subsequent 12 hours. In culture, the internalization of these particles was relevantly accelerated and intensified after trophoblast activation by IFN-γ (Albieri et al, 2001;Amarante-Paffaro et al, 2004). Furthermore, comparatively to zymosan, Escherichia coli particles were internalized by placental trophoblast more rapidly, suggesting that phagocytosis may depend on the nature of the target organism and possibly to specific patterns of recognition (Amarante-Paffaro et al, 2004).…”

“…In culture, the internalization of these particles was relevantly accelerated and intensified after trophoblast activation by IFN-γ (Albieri et al, 2001;Amarante-Paffaro et al, 2004). Furthermore, comparatively to zymosan, Escherichia coli particles were internalized by placental trophoblast more rapidly, suggesting that phagocytosis may depend on the nature of the target organism and possibly to specific patterns of recognition (Amarante-Paffaro et al, 2004). The mechanism by which trophoblast cells can recognize phagocytic particles remains to be defined.…”

MAPK-activated Protein Kinase 2 Differentially Regulates Plasmodium falciparum Glycosylphosphatidylinositol-induced Production of Tumor Necrosis Factor-α and Interleukin-12 in Macrophages

“…In the absence of prior immunity, these proinflammatory mediators function as the first line of defense against parasites and are crucial for controlling infection; otherwise, parasites grow rapidly and overwhelm the host, causing severe illness and fatality. The inflammatory mediators exert toxic effects on parasites by initiating a variety of effector mechanisms, such as cytotoxicity by free radicals, phagocytosis, complement activation, and cell and antibody-mediated adaptive immune responses (5,9,(11)(12)(13). For example, IFN-␥ is a potent immunostimulatory cytokine that primes macrophages for the efficient production of cyto-kines, including TNF-␣, IL-12, IL-6, and reactive oxygen and nitrogen free radicals.…”

Complement component C3 functions as an embryotrophic factor in early postimplantation rat embryos

“…It has been shown that C3b bound to membrane cofactor protein (MCP), or C3-like factor bound to complement receptors CR1 and CR3 is involved in the fertilization of humans and frogs (Anderson et al, 1993;Cervoni et al, 1992;Llanos et al, 2000). Phagocytic activity in mouse placental trophoblasts is enhanced by C3b probably through CR1 (Albieri et al, 1999;Amarante-Paffaro et al, 2004). Furthermore, embryotrophic function of iC3b, the cleaved product of C3b, in mouse blastocysts probably through the rodent complement receptor-related protein y (Crry) and CR3 has been reported (Lee et al, 2004).…”