Annexin A1 peptide is able to induce an anti-parasitic effect in human placental explants infected by Toxoplasma gondii.

This study was conducted to investigate annexin A1 (ANXA1) functions in human placental explants infected with Toxoplasma gondii (T. gondii). We examined the first and third trimester placental explants infected with T. gondii (n = 7 placentas/group) to identify the number and location of parasites, ANXA1 protein, potential involvement of formyl peptide receptors (FPR1 and FPR2), and COX-2 expressions by immunohistochemistry. Treatments with Ac2-26 mimetic peptide of ANXA1 were performed to verify the parasitism rate (ß-galactosidase assay), prostaglandin E2 levels (ELISA assay), and ANXA1, FPR1 and COX-2 expression in third trimester placentas. Placental explants of third trimester expressed less ANXA1 and were more permissive to T. gondii infection than first trimester placentas that expressed more ANXA1. Ac2-26 treatment increases endogenous ANXA1 and decreases parasitism rate, COX-2, and prostaglandin E2 levels. Altogether, these data provide further insight into the anti-parasitic and anti-inflammatory effects of ANXA1 in placentas infected with T. gondii.

Effect of macrophage migration inhibitory factor (MIF) in human placental explants infected with Toxoplasma gondii depends on gestational age.

Because macrophage migration inhibitory factor (MIF) is a key cytokine in pregnancy and has a role in inflammatory response and pathogen defense, the objective of the present study was to investigate the effects of MIF in first- and third-trimester human placental explants infected with Toxoplasma gondii. Explants were treated with recombinant MIF, IL-12, interferon-γ, transforming growth factor-ß1, or IL-10, followed by infection with T. gondii RH strain tachyzoites. Supernatants of cultured explants were assessed for MIF production. Explants were processed for morphologic analysis, immunohistochemistry, and real-time PCR analysis. Comparison of infected and stimulated explants versus noninfected control explants demonstrated a significant increase in MIF release in first-trimester but not third-trimester explants. Tissue parasitism was higher in third- than in first-trimester explants. Moreover, T. gondii DNA content was lower in first-trimester explants treated with MIF compared with untreated explants. However, in third-trimester explants, MIF stimulus decreased T. gondii DNA content only at the highest concentration of the cytokine. In addition, high expression of MIF receptor was observed in first-trimester placental explants, whereas MIF receptor expression was low in third-trimester explants. In conclusion, MIF was up-regulated and demonstrated to be important for control of T. gondii infection in first-trimester explants, whereas lack of MIF up-regulation in third-trimester placentas may be involved in higher susceptibility to infection at this gestational age.

Macrophage migration inhibitory factor is up-regulated in human first-trimester placenta stimulated by soluble antigen of Toxoplasma gondii, resulting in increased monocyte adhesion on villous explants.

Considering the potential role of macrophage migration inhibitory factor (MIF) in the inflammation process in placenta when infected by pathogens, we investigated the production of this cytokine in chorionic villous explants obtained from human first-trimester placentas stimulated with soluble antigen from Toxoplasma gondii (STAg). Parallel cultures were performed with villous explants stimulated with STAg, interferon-gamma (IFN-gamma), or STAg plus IFN-gamma. To assess the role of placental MIF on monocyte adhesiveness to human trophoblast, explants were co-cultured with human myelomonocytic THP-1 cells in the presence or absence of supernatant from cultures treated with STAg (SPN), SPN plus anti-MIF antibodies, or recombinant MIF. A significantly higher concentration of MIF was produced and secreted by villous explants treated with STAg or STAg plus IFN-gamma after 24-hour culture. Addition of SPN or recombinant MIF was able to increase THP-1 adhesion, which was inhibited after treatment with anti-MIF antibodies. This phenomenon was associated with intercellular adhesion molecule expression by villous explants. Considering that the processes leading to vertical dissemination of T. gondii remain widely unknown, our results demonstrate that MIF production by human first-trimester placenta is up-regulated by parasite antigen and may play an essential role as an autocrine/paracrine mediator in placental infection by T. gondii.

Potential role of interleukin-1 at the peri-ovulation stage in a species of placental viviparous reptile, the three-toed skink, Chalcides chalcides (Squamata: Scincidae).

We recently showed that interleukin-1 (IL-1) is secreted by the placenta of a species of squamate reptile, the three-toed skink, Chalcides chalcides. In this study, we used immunohistochemical techniques to investigate the expression of IL-1 (in the two isoforms, IL-1alpha and IL-1beta) and its specific membrane receptor IL-1 RtI in uterine oviduct during the peri-implantation period. We found that both IL-1 and its receptor were expressed in uterine tissues before and after ovulation (in the pre-ovulatory stage, even before the yolk had formed in the ovary). However, while IL-1alpha was mostly localized in the uterine mesenchyme tissue, IL-1beta and IL-1RtI were present in the uterine epithelium. Our data provide a further comparison between the reproduction of mammals and squamate reptiles.