title: Coxiella burnetii Infects Primary Bovine Macrophages and Limits Their Host Cell Response.
abstract: Although domestic ruminants have long been recognized as the main source of human Q fever, little is known about the lifestyle that the obligate intracellular Gram-negative bacterium Coxiella burnetii adopts in its animal host. Because macrophages are considered natural target cells of the pathogen, we established primary bovine monocyte-derived macrophages (MDM) as an in vitro infection model to study reservoir host-pathogen interactions at the cellular level. In addition, bovine alveolar macrophages were included to take cell type peculiarities at a host entry site into account. Cell cultures were inoculated with the virulent strain Nine Mile I (NMI; phase I) or the avirulent strain Nine Mile II (NMII; phase II). Macrophages from both sources internalized NMI and NMII. MDM were particularly permissive for NMI internalization, but NMI and NMII replicated with similar kinetics in these cells. MDM responded to inoculation with a general upregulation of Th1-related cytokines such as interleukin-1β (IL-1β), IL-12, and tumor necrosis factor alpha (TNF-α) early on (3 h postinfection). However, inflammatory responses rapidly declined when C. burnetii replication started. C. burnetii infection inhibited translation and release of IL-1β and vastly failed to stimulate increased expression of activation markers, such as CD40, CD80, CD86, and major histocompatibility complex (MHC) molecules. Such capability of limiting proinflammatory responses may help Coxiella to protect itself from clearance by the host immune system. The findings provide the first detailed insight into C. burnetii-macrophage interactions in ruminants and may serve as a basis for assessing the virulence and the host adaptation of C. burnetii strains.
authors.affiliation: Friedrich-Loeffler-Institut (FLI), Institute of Molecular Pathogenesis, Jena, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Sobotta
authors.affiliation: Friedrich-Loeffler-Institut (FLI), Institute of Molecular Pathogenesis, Jena, Germany.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Hillarius
authors.affiliation: Friedrich-Loeffler-Institut (FLI), Institute of Molecular Pathogenesis, Jena, Germany.
authors.forename: Marvin
authors.initials: M
authors.lastname: Mager
authors.affiliation: Institute for Hygiene and Infectious Diseases of Animals, Justus-Liebig-University (JLU), Giessen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kerner
authors.affiliation: Institute for Hygiene and Infectious Diseases of Animals, Justus-Liebig-University (JLU), Giessen, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Heydel
authors.affiliation: Friedrich-Loeffler-Institut (FLI), Institute of Molecular Pathogenesis, Jena, Germany christian.menge@fli.bund.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Menge
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D002417:Cattle; D016997:Coxiella burnetii / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D004197:Disease Reservoirs; D005786:Gene Expression Regulation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology*; D061251:Primary Cell Culture; D015398:Signal Transduction; D013045:Species Specificity; D058408:Th1-Th2 Balance; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014774:Virulence
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12