title: Characterization of a caprine model for the subclinical initial phase of Mycobacterium avium subsp. paratuberculosis infection.
abstract: BACKGROUND
  Paratuberculosis caused by Mycobacterium avium subsp. paratuberculosis (MAP) is difficult to control due to a long phase of clinically non-apparent (latent) infection for which sensitive diagnostics are lacking. A defined animal model for this phase of the infection can help to investigate host-MAP interactions in apparently healthy animals and identify surrogate markers for disease progress and might also serve as challenge model for vaccines. To establish such a model in goats, different age at inoculation and doses of oral inoculum of MAP were compared. Clinical signs, faecal shedding as well as MAP-specific antibody, IFN-γ and IL-10 responses were used for in vivo monitoring. At necropsy, about one year after inoculation (pi), pathomorphological findings and bacterial organ burden (BOB) were scored.
  
  
  RESULTS
  MAP infection manifested in 26/27 inoculated animals irrespective of age at inoculation and dose. Clinical signs developed in three goats. Faecal shedding, IFN-γ and antibody responses emerged 6, 10-14 and 14 wpi, respectively, and continued with large inter-individual variation. One year pi, lesions were detected in 26 and MAP was cultured from tissues of 23 goats. Positive animals subdivided in those with high and low overall BOB. Intestinal findings resembled paucibacillary lesions in 23 and multibacillary in 4 goats. Caseous and calcified granulomas predominated in intestinal LNN. BOB and lesion score corresponded well in intestinal mucosa and oGALT but not in intestinal LNN.
  
  
  CONCLUSIONS
  A defined experimental infection model for the clinically non-apparent phase of paratuberculosis was established in goats as suitable basis for future studies.
authors.affiliation: Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany. heike.koehler@fli.bund.de.
authors.forename: Heike
authors.initials: H
authors.lastname: Köhler
authors.affiliation: Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany. asoschinka@web.de.|Present address: Tierärztliche GmbH Hagenow, Hagenow, Germany. asoschinka@web.de.
authors.forename: Anneka
authors.initials: A
authors.lastname: Soschinka
authors.affiliation: Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany. meneguana@gmx.de.|Present address: Tierarztpraxis Dr. Peitzmeier, Hille, Germany. meneguana@gmx.de.
authors.forename: Michaela
authors.initials: M
authors.lastname: Meyer
authors.affiliation: Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany. angela.kather@web.de.|Present address: Institute of Immunology, Jena University Hospital, Jena, Germany. angela.kather@web.de.
authors.forename: Angela
authors.initials: A
authors.lastname: Kather
authors.affiliation: Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany. petra.reinhold@fli.bund.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Reinhold
authors.affiliation: Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany. elisabeth.liebler-tenorio@fli.bund.de.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Liebler-Tenorio
mesh_terms: D000818:Animals; D000917:Antibody Formation; D058345:Asymptomatic Infections; D057138:Bacterial Shedding; D018450:Disease Progression; D015511:Goat Diseases / Q000382:microbiology* / Q000473:pathology; D006041:Goats / Q000382:microbiology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008198:Lymph Nodes / Q000382:microbiology / Q000473:pathology; D008297:Male; D016927:Mycobacterium avium subsp. paratuberculosis; D010283:Paratuberculosis / Q000382:microbiology / Q000473:pathology*; D010581:Peyer's Patches / Q000382:microbiology / Q000473:pathology
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma