title: In vitro infection of bovine monocytes with Mycoplasma bovis delays apoptosis and suppresses production of gamma interferon and tumor necrosis factor alpha but not interleukin-10.
abstract: Mycoplasma bovis is one of the major causative pathogens of bovine respiratory complex disease (BRD), which is characterized by enzootic pneumonia, mastitis, pleuritis, and polyarthritis. M. bovis enters and colonizes bovine respiratory epithelial cells through inhalation of aerosol from contaminated air. The nature of the interaction between M. bovis and the bovine innate immune system is not well understood. We hypothesized that M. bovis invades blood monocytes and regulates cellular function to support its persistence and systemic dissemination. We used bovine-specific peptide kinome arrays to identify cellular signaling pathways that could be relevant to M. bovis-monocyte interactions in vitro. We validated these pathways using functional, protein, and gene expression assays. Here, we show that infection of bovine blood monocytes with M. bovis delays spontaneous or tumor necrosis factor alpha (TNF-α)/staurosporine-driven apoptosis, activates the NF-κB p65 subunit, and inhibits caspase-9 activity. We also report that M. bovis-infected bovine monocytes do not produce gamma interferon (IFN-γ) and TNF-α, although the level of production of interleukin-10 (IL-10) is elevated. Our findings suggest that M. bovis takes over the cellular machinery of bovine monocytes to prolong bacterial survival and to possibly facilitate subsequent systemic distribution.
authors.affiliation: Vaccine and Infectious Disease Organization-International Vaccine Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Musa
authors.initials: M
authors.lastname: Mulongo
authors.forename: Tracy
authors.initials: T
authors.lastname: Prysliak
authors.forename: Erin
authors.initials: E
authors.lastname: Scruten
authors.forename: Scott
authors.initials: S
authors.lastname: Napper
authors.forename: Jose
authors.initials: J
authors.lastname: Perez-Casal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology* / Q000502:physiology; D053453:Caspase 9 / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D009175:Mycoplasma Infections / Q000276:immunology*; D045682:Mycoplasma bovis / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014380:Tuberculosis, Bovine / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D053453:Caspase 9