title: Effect of macrophage migration inhibitory factor (MIF) in human placental explants infected with Toxoplasma gondii depends on gestational age.
abstract: 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.
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors.forename: Angelica
authors.initials: A
authors.lastname: de Oliveira Gomes
authors.forename: Deise Aparecida
authors.initials: DA
authors.lastname: de Oliveira Silva
authors.forename: Neide Maria
authors.initials: NM
authors.lastname: Silva
authors.forename: Bellisa
authors.initials: B
authors.lastname: de Freitas Barbosa
authors.forename: Priscila Silva
authors.initials: PS
authors.lastname: Franco
authors.forename: Mariana Bodini
authors.initials: MB
authors.lastname: Angeloni
authors.forename: Marise Lopes
authors.initials: ML
authors.lastname: Fermino
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Roque-Barreira
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bechi
authors.forename: Luana Ricci
authors.initials: LR
authors.lastname: Paulesu
authors.forename: Maria Célia
authors.initials: MC
authors.lastname: Dos Santos
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Mineo
authors.forename: Eloisa Amália Vieira
authors.initials: EA
authors.lastname: Ferro
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005865:Gestational Age; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D008954:Models, Biological; D009573:Nitrites / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology* / Q000473:pathology; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000187:drug effects; D011263:Pregnancy Trimester, Third / Q000187:drug effects; D014122:Toxoplasma / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014123:Toxoplasmosis / Q000469:parasitology* / Q000473:pathology / Q000517:prevention & control
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; D009573:Nitrites; C045084:invariant chain; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human