Effect of Macrophage Migration Inhibitory Factor (MIF) in Human Placental Explants Infected with Toxoplasma gondii Depends on Gestational Age

• Published in: The American journal of pathology Vol. 178; no. 6; pp. 2792 - 2801
• Main Authors: de Oliveira Gomes, Angelica, de Oliveira Silva, Deise Aparecida, Silva, Neide Maria, de Freitas Barbosa, Bellisa, Franco, Priscila Silva, Angeloni, Mariana Bodini, Fermino, Marise Lopes, Roque-Barreira, Maria Cristina, Bechi, Nicoletta, Paulesu, Luana Ricci, dos Santos, Maria Célia, Mineo, José Roberto, Ferro, Eloisa Amália Vieira
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.06.2011; American Society for Investigative Pathology
• Subjects: Antigens, Differentiation, B-Lymphocyte - genetics; Antigens, Differentiation, B-Lymphocyte - metabolism; Biological and medical sciences; Female; Gene Expression Regulation; Gestational Age; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - metabolism; Human protozoal diseases; Humans; Infectious diseases; Intramolecular Oxidoreductases - biosynthesis; Intramolecular Oxidoreductases - metabolism; Intramolecular Oxidoreductases - pharmacology; Investigative techniques, diagnostic techniques (general aspects); Macrophage Migration-Inhibitory Factors - biosynthesis; Macrophage Migration-Inhibitory Factors - metabolism; Macrophage Migration-Inhibitory Factors - pharmacology; Medical sciences; Models, Biological; Nitrites - metabolism; Parasitic diseases; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Placenta - drug effects; Placenta - metabolism; Placenta - parasitology; Placenta - pathology; Pregnancy; Pregnancy Trimester, First - drug effects; Pregnancy Trimester, Third - drug effects; Protozoal diseases; Regular; Toxoplasma - cytology; Toxoplasma - drug effects; Toxoplasma - physiology; Toxoplasmosis; Toxoplasmosis - parasitology; Toxoplasmosis - pathology; Toxoplasmosis - prevention & control; Human; Protozoa; Apicomplexa; Protozoal disease; Fetal membrane; Explant; Parasitosis; Gestational age; Infection; Macrophage migration inhibitory factor; Anatomic pathology; Placenta; Toxoplasma gondii; Toxoplasmosis; Developmental stage
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2011.02.005

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-β1, 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.