title: Monocyte-derived dendritic cells from late gestation cows have an impaired ability to mature in response to E. coli stimulation in a receptor and cytokine-mediated fashion.
abstract: During late gestation the bovine immune system is less capable of eliciting inflammatory responses and eliminating invading pathogens. The maternal immune system is directed toward tolerance in order to prevent fetal rejection due to recognition of paternal antigens. In humans and mice, dendritic cell (DC) populations maintain a tolerogenic phenotype essential in the generation and preservation of maternal immune tolerance throughout pregnancy. However, the primary mechanisms which facilitate maternal immune tolerance involved in bovine gestation remain poorly understood. In order to determine if DC phenotype and function were regulated toward tolerance during bovine gestation, we compared in vitro generated monocyte-derived DC (mo-DC) from monocytes isolated from cows in late gestation (LG) to those from non-pregnant (NP) cows in their ability to mature following stimulation with UV irradiated Escherichia coli. Our results show mo-DC from LG cows have an impaired ability to mature in response to E. coli stimulation in a receptor and cytokine-mediated fashion in comparison to those from NP cows. Specifically, mo-DC from LG cows were unable to upregulate MHC II and maintained high expression of CD14, both indicative of an immature phenotype following E. coli-stimulation. Only mo-DC from LG showed significant increase in IL-10 production and had a significantly lower ratio of production of the Th1-polarizing cytokine IL-12 to regulatory cytokine IL-10 following E. coli stimulation compared to mo-DC from NP cows. Our findings demonstrate mo-DC from LG cows have a stifled capacity to develop a mature phenotype and drive pro-inflammatory Th1-type responses to E. coli stimulation. Results from this study provide insight into DC immune modulation in bovine pregnancy and elucidate host factors which may contribute to the heightened susceptibility to infection in late gestation.
authors.affiliation: Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. Electronic address: bjp62@cornell.edu.
authors.forename: Brianna
authors.initials: B
authors.lastname: Pomeroy
authors.affiliation: Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Anja
authors.initials: A
authors.lastname: Sipka
authors.affiliation: Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Klaessig
authors.affiliation: Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA; GD Animal Health, Deventer, The Netherlands.
authors.forename: Ynte
authors.initials: Y
authors.lastname: Schukken
mesh_terms: D000818:Animals; D002417:Cattle / Q000276:immunology*; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000150:complications / Q000276:immunology; D005260:Female; D005865:Gestational Age; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology; D011270:Pregnancy, Animal / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018950:Lipopolysaccharide Receptors; D016753:Interleukin-10; D018664:Interleukin-12
keywords: Bovine; Dendritic cells; E. coli; Late gestation; Maturation