title: Differential macrophage function in Brown Swiss and Holstein Friesian cattle.
abstract: There is strong evidence that high yielding dairy cows are extremely susceptible to infectious diseases, and that this has severe economic consequences for the dairy industry and welfare implications. Here we present preliminary functional evidence showing that the innate immune response differs between cow breeds. The ability of macrophages (MØ) to kill pathogens depends in part on oxygen-dependent and independent mechanisms. The oxygen-dependent mechanisms rely on the generation of reactive oxygen and nitrogen species (ROS/RNS, respectively). ROS production has been shown to activate the inflammasome complex in MØ leading to increased production of the pro-inflammatory cytokine Interleukin-1β (IL-1β). Conversely RNS inhibits inflammasome mediated IL-1β activation, indicating a division between inflammasome activation and RNS production. In the present study MØ from Brown Swiss (BS) cattle produce significantly more RNS and less IL-1β when compared to cells from Holstein Friesian (HF) cattle in response to bacterial or fungal stimuli. Furthermore, BS MØ killed ingested Salmonella typhimurium more efficiently, supporting anecdotal evidence of increased disease resistance of the breed. Inhibition of autophagy by 3-methyladenine (3-MA) stimulated IL-1β secretion in cells from both breeds, but was more pronounced in HF MØ. Blocking RNS production by l-arginase completely abolished RNS production but increased IL-1β secretion in BS MØ. Collectively these preliminary data suggest that the dichotomy of inflammasome activation and RNS production exists in cattle and differs between these two breeds. As pattern recognition receptors and signaling pathways are involved in the assessed functional differences presented herein, our data potentially aid the identification of in vitro predictors of appropriate innate immune response. Finally, these predictors may assist in the discovery of candidate genes conferring increased disease resistance for future use in combination with known production traits.
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Amanda Jane
authors.initials: AJ
authors.lastname: Gibson
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Woodman
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pennelegion
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Patterson
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Stuart
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: Hosker
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Siviter
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Chloe
authors.initials: C
authors.lastname: Douglas
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Whitehouse
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Will
authors.initials: W
authors.lastname: Wilkinson
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK.
authors.forename: Sherri-Anne
authors.initials: SA
authors.lastname: Pegg
authors.affiliation: Animal and Plant Health Agency, Bovine TB, Weybridge, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Villarreal-Ramos
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, AL9 7TA, UK. Electronic address: dwerling@rvc.ac.uk.
authors.forename: Dirk
authors.initials: D
authors.lastname: Werling
mesh_terms: D000818:Animals; D001947:Breeding; D002417:Cattle / Q000276:immunology*; D007113:Immunity, Innate; D020382:Interleukin-18 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D020382:Interleukin-18; D053583:Interleukin-1beta; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide
keywords: Cattle breeds; Inflammasome; Innate immunity; Macrophages; ROS