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Infection and Immunity, October 2003, p. 5831-5844, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.5831-5844.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Experimental Mycobacterium tuberculosis Infection of Cynomolgus Macaques Closely Resembles the Various Manifestations of Human M. tuberculosis Infection

Saverio V. Capuano III,1,2 Denise A. Croix,1,{dagger} Santosh Pawar,1 Angelica Zinovik,1 Amy Myers,1 Philana L. Lin,3 Stephanie Bissel,4 Carl Fuhrman,5 Edwin Klein,6 and JoAnne L. Flynn1*

Departments of Molecular Genetics and Biochemistry,1 Obstetrics, Gynecology, and Reproductive Sciences,2 Pathology ,4 Radiology,5 Division of Laboratory Animal Resources, University of Pittsburgh School of Medicine,6 Department of Pediatrics, Children's Hospital, Pittsburgh, Pennsylvania 152613

Received 28 February 2003/ Returned for modification 6 May 2003/ Accepted 21 July 2003

Nonhuman primates were used to develop an animal model that closely mimics human Mycobacterium tuberculosis infection. Cynomolgus macaques were infected with low doses of virulent M. tuberculosis via bronchoscopic instillation into the lung. All monkeys were successfully infected, based on tuberculin skin test conversion and peripheral immune responses to M. tuberculosis antigens. Progression of infection in the 17 monkeys studied was variable. Active-chronic infection, observed in 50 to 60% of monkeys, was characterized by clear signs of infection or disease on serial thoracic radiographs and in other tests and was typified by eventual progression to advanced disease. Approximately 40% of monkeys did not progress to disease in the 15 to 20 months of study, although they were clearly infected initially. These monkeys had clinical characteristics of latent tuberculosis in humans. Low-dose infection of cynomolgus macaques appears to represent the full spectrum of human M. tuberculosis infection and will be an excellent model for the study of pathogenesis and immunology of this infection. In addition, this model will provide an opportunity to study the latent M. tuberculosis infection observed in ~90% of all infected humans.

* Corresponding author. Mailing address: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, W1157 Biomedical Science Tower, Pittsburgh, PA 15261. Phone: (412) 624-7743. Fax: (412) 648-3394. E-mail: joanne{at}pitt.edu.

Editor: V. J. DiRita

{dagger} Present address: Miltenyi Biotec, Inc., Auburn, CA 95602.

Infection and Immunity, October 2003, p. 5831-5844, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.5831-5844.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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