Animal model of Mycobacterium abscessus lung infection.
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.
Ordway
Diane
D
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA. D.Ordway-Rodriguez@colostate.edu
Henao-Tamayo
Marcela
M
Smith
Erin
E
Shanley
Crystal
C
Harton
Marisa
M
Troudt
Jolynn
J
Bai
Xiyuan
X
Basaraba
Randall J
RJ
Orme
Ian M
IM
Chan
Edward D
ED
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D007371:Interferon-gamma / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009164:Mycobacterium Infections / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma