title: Very Low Doses of Mycobacterium tuberculosis Yield Diverse Host Outcomes in Common Marmosets (Callithrix jacchus).
abstract: Identifying and refining small-animal models of tuberculosis that recapitulate aspects of human Mycobacterium tuberculosis infection can contribute to advancing our understanding of critical facets of the disease. To study the effects of very low-dose infections with 2 strains of M. tuberculosis on disease progression and survival in common marmosets, animals were challenged with strains Erdman and CDC1551 at doses ranging from 1 to 12 cfu. These data revealed that the susceptibility of marmosets to M. tuberculosis infection is influenced by strain virulence and initial dose. Marmoset infection with the Erdman strain, even at very low doses, resulted in rapid disease progression associated with severe weight loss, extensive pathology, and poor survival. By contrast, challenge with the less virulent CDC1551 strain resulted in slower disease progression, delayed weight loss, and prolonged survival. One marmoset infected with CDC1551 at a very low dose (approximately 1 cfu) was able to contain and control M. tuberculosis infection in a subclinical state that persisted as long as 300 d. These findings underscore the critical importance of understanding the heterogeneity in host outcome that can arise in association with different infectious doses and strains in the marmoset model of tuberculosis.
authors: Department of Microbiology and Molecular Genetics, Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Anthony M
authors: AM
authors: Cadena
authors: Division of Laboratory Animal Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Edwin C
authors: EC
authors: Klein
authors: Department of Microbiology and Molecular Genetics, Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Alexander G
authors: AG
authors: White
authors: Department of Microbiology and Molecular Genetics, Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Jaime A
authors: JA
authors: Tomko
authors: Department of Microbiology and Molecular Genetics, Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Chelsea L
authors: CL
authors: Chedrick
authors: Center for Vaccine Research, Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Douglas S
authors: DS
authors: Reed
authors: Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA; Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors: Laura E
authors: LE
authors: Via
authors: Division of Infectious Diseases, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Philana Ling
authors: PL
authors: Lin
authors: Department of Microbiology and Molecular Genetics, Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. joanne@pitt.edu.
authors: JoAnne L
authors: JL
authors: Flynn
mesh_terms: D000818:Animals; D002144:Callithrix / Q000382:microbiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D054884:Host-Pathogen Interactions; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity; D000072078:Positron Emission Tomography Computed Tomography; D014376:Tuberculosis / Q000000981:diagnostic imaging / Q000382:microbiology* / Q000473:pathology; D014774:Virulence