title: Pivotal role for monocytes/macrophages and dendritic cells in maternal immune response to the developing embryo in cattle.
abstract: In mammals, successful pregnancy is dependent in part on the adaptation or regulation of the maternal immune system to prevent the rejection of the embryonic semiallograft. A modification in Th cell function and secretion is a requirement for the establishment and maintenance of pregnancy. Although there is strong evidence from studies in humans and mice linking successful pregnancy with the predominance of Th2-type immunity, the situation in cattle remains unclear. This study describes the characterization of the immune response of the bovine maternal endometrium to the presence of a developing embryo, with specific emphasis on the macrophage and dendritic cell populations and associated factors, using quantitative real-time PCR, in situ hybridization, and immunohistochemistry. Furthermore, in vivo and in vitro models were developed to investigate the potential role of progesterone and interferon-tau (IFNT) in the regulation of these immune factors. There was a marked increase in the population of CD14(+) cells and CD172a-CD11c(+) cells in the endometrium in response to pregnancy, which was paralleled by increased mRNA expression of a number of non-Th-associated factors, including IL12B and IL15, and downregulation of IL18. In addition, we identified several novel IFNT- and progesterone-regulated factors, including IL12B, MCP1, MCP2, PTX3, RSAD2, and TNFA, whose regulation may be critical to pregnancy outcome. Our findings give center stage to non-Th cells, such as monocytes/macrophages and dendritic cells, in the bovine immune response to the semiallogenic embryo. In conclusion, we propose that in cattle, successful pregnancy establishment is associated with a dramatic regulation of the cytokine network, primarily by endometrial monocytes/macrophages and dendritic cells.
authors.affiliation: School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Dublin, Ireland.
authors.forename: Nadéra
authors.initials: N
authors.lastname: Mansouri-Attia
authors.forename: Lilian J
authors.initials: LJ
authors.lastname: Oliveira
authors.forename: Niamh
authors.initials: N
authors.lastname: Forde
authors.forename: Alan G
authors.initials: AG
authors.lastname: Fahey
authors.forename: John A
authors.initials: JA
authors.lastname: Browne
authors.forename: James F
authors.initials: JF
authors.lastname: Roche
authors.forename: Olivier
authors.initials: O
authors.lastname: Sandra
authors.forename: Pierrette
authors.initials: P
authors.lastname: Reinaud
authors.forename: Patrick
authors.initials: P
authors.lastname: Lonergan
authors.forename: Trudee
authors.initials: T
authors.lastname: Fair
mesh_terms: D000818:Animals; D002417:Cattle / Q000276:immunology*; D016207:Cytokines / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000276:immunology*; D047108:Embryonic Development; D004717:Endometrium / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007370:Interferon Type I / Q000502:physiology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000502:physiology; D011374:Progesterone / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C020947:interferon tau; D011374:Progesterone