Animal model of Mycobacterium abscessus lung infection.

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.

DOI: 10.1189/jlb.1007696
0102020102011201220132014201520162017
Citations per Year

69 Citations

Semantic Scholar estimates that this publication has 69 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Ordway2008AnimalMO, title={Animal model of Mycobacterium abscessus lung infection.}, author={Diane J. Ordway and Marcela I Henao-Tamayo and Erin E. Smith and Crystal A. Shanley and Marisa R. Harton and Jolynn M Troudt and Xiyuan Bai and Randall J Basaraba and Ian M. Orme and Edward D . Chan}, journal={Journal of leukocyte biology}, year={2008}, volume={83 6}, pages={1502-11} }