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Originally published online as doi:10.1189/jlb.1007696 on February 29, 2008

Published online before print February 29, 2008
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(Journal of Leukocyte Biology. 2008;83:1502-1511.)
© 2008 by Society for Leukocyte Biology

Animal model of Mycobacterium abscessus lung infection

Diane Ordway*,1, Marcela Henao-Tamayo*, Erin Smith*, Crystal Shanley*, Marisa Harton*, JoLynn Troudt*, Xiyuan Bai{dagger}, Randall J. Basaraba*, Ian M. Orme* and Edward D. Chan{dagger},{ddagger},§

* Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA;
{ddagger} Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Denver, Colorado, USA;
{dagger} National Jewish Medical and Research Center, Denver, Colorado, USA; and
§ Denver Veterans Affairs Medical Center, Denver, Colorado, USA

1Correspondence: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA. E-mail: D.Ordway-Rodriguez{at}colostate.edu

ABSTRACT

Chronic lung disease as a result of Mycobacterium abscessus is an emerging infection in the United States. We characterized the lung immune responses in mice and guinea pigs infected with M. abscessus. C57BL/6 and leptin-deficient ob/ob mice challenged with a low-dose aerosol (LDA) of M. abscessus did not develop an infection. However, when challenged with a high-dose aerosol (HDA), C57BL/6 and ob/ob mice developed an established infection and a pulmonary immune response consisting of an early influx of IFN-{gamma}+ CD4+ T cells; this immune response preceded the successful clearance of M. abscessus in both strains of mice, although mycobacterial elimination was delayed in the ob/ob mice. Infected guinea pigs showed an increased influx of lymphocytes into the lungs with bacterial clearance by Day 60. In contrast to the C57BL/6 and ob/ob mice and guinea pigs, IFN-{gamma} knockout (GKO) mice challenged with a LDA or HDA of M. abscessus showed a progressive lung infection despite a robust influx of T cells, macrophages, and dendritic cells, culminating in extensive lung consolidation. Furthermore, with HDA challenge of the GKO mice, emergence of IL-4- and IL-10-producing CD4+ and CD8+ T cells was seen in the lungs. In conclusion, IFN-{gamma} is critically important in the host defense against M. abscessus. As the number of effective drugs against M. abscessus is limited, the GKO mice provide a model for in vivo testing of novel drugs.

Key Words: T cells • dendritic cells • macrophages • cytokines






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