title: Brucella canis is an intracellular pathogen that induces a lower proinflammatory response than smooth zoonotic counterparts.
abstract: Canine brucellosis caused by Brucella canis is a disease of dogs and a zoonotic risk. B. canis harbors most of the virulence determinants defined for the genus, but its pathogenic strategy remains unclear since it has not been demonstrated that this natural rough bacterium is an intracellular pathogen. Studies of B. canis outbreaks in kennel facilities indicated that infected dogs displaying clinical signs did not present hematological alterations. A virulent B. canis strain isolated from those outbreaks readily replicated in different organs of mice for a protracted period. However, the levels of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-12 in serum were close to background levels. Furthermore, B. canis induced lower levels of gamma interferon, less inflammation of the spleen, and a reduced number of granulomas in the liver in mice than did B. abortus. When the interaction of B. canis with cells was studied ex vivo, two patterns were observed, a predominant scattered cell-associated pattern of nonviable bacteria and an infrequent intracellular replicative pattern of viable bacteria in a perinuclear location. The second pattern, responsible for the increase in intracellular multiplication, was dependent on the type IV secretion system VirB and was seen only if the inoculum used for cell infections was in early exponential phase. Intracellular replicative B. canis followed an intracellular trafficking route undistinguishable from that of B. abortus. Although B. canis induces a lower proinflammatory response and has a stealthier replication cycle, it still displays the pathogenic properties of the genus and the ability to persist in infected organs based on the ability to multiply intracellularly.
authors.affiliation: Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Carlos
authors.initials: C
authors.lastname: Chacón-Díaz
authors.affiliation: Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Pamela
authors.initials: P
authors.lastname: Altamirano-Silva
authors.affiliation: Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Gabriela
authors.initials: G
authors.lastname: González-Espinoza
authors.affiliation: Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.
authors.forename: María-Concepción
authors.initials: MC
authors.lastname: Medina
authors.affiliation: Departamento de Patología, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Alfaro-Alarcón
authors.affiliation: Laboratorio de Análisis Clínicos, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.
authors.forename: Laura
authors.initials: L
authors.lastname: Bouza-Mora
authors.affiliation: Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.
authors.forename: César
authors.initials: C
authors.lastname: Jiménez-Rojas
authors.affiliation: Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Melissa
authors.initials: M
authors.lastname: Wong
authors.affiliation: Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.
authors.forename: Elías
authors.initials: E
authors.lastname: Barquero-Calvo
authors.affiliation: Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Norman
authors.initials: N
authors.lastname: Rojas
authors.affiliation: Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.
authors.forename: Caterina
authors.initials: C
authors.lastname: Guzmán-Verri
authors.affiliation: Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica emoreno@racsa.co.cr esteban.chaves@ucr.ac.cr.
authors.forename: Edgardo
authors.initials: E
authors.lastname: Moreno
authors.affiliation: Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica emoreno@racsa.co.cr esteban.chaves@ucr.ac.cr.
authors.forename: Esteban
authors.initials: E
authors.lastname: Chaves-Olarte
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D002003:Brucella abortus / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D041002:Brucella canis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D002006:Brucellosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004285:Dogs; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013045:Species Specificity; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D000069319:Type IV Secretion Systems / Q000235:genetics / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000069319:Type IV Secretion Systems; D018664:Interleukin-12; D007371:Interferon-gamma