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Infection and Immunity, October 2002, p. 5556-5561, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5556-5561.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Differential Responses of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium

Douglas J. Weiss,* Oral A. Evanson, Andreas Moritz, Ming Qi Deng, and Mitchell S. Abrahamsen

Department of Veterinary Pathobiology, University of Minnesota, St. Paul, Minnesota 55108

Received 5 March 2002/ Returned for modification 2 May 2002/ Accepted 5 July 2002

Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium are antigenically and genetically similar organisms; however, they differ in their virulence for cattle. M. avium subsp. paratuberculosis causes a chronic intestinal infection leading to a chronic wasting disease termed paratuberculosis or Johne's disease, whereas M. avium subsp. avium causes only a transient infection. We compared the response of bovine monocyte-derived macrophages to ingestion of M. avium subsp. paratuberculosis and M. avium subsp. avium organisms by determining organism survival, superoxide and nitric oxide production, and expression of the cytokines tumor necrosis factor alpha (TNF-{alpha}), gamma interferon (IFN-{gamma}), interleukin-8 (IL-8), IL-10, IL-12, and granulocyte-monocyte colony-stimulating factor (GM-CSF). Unlike M. avium subsp. paratuberculosis, macrophages were able to kill approximately half of the M. avium subsp. avium organisms after 96 h of incubation. This difference in killing efficiency was not related to differences in nitric oxide or superoxide production. Compared to macrophages activated with IFN-{gamma} and lipopolysaccharide, macrophages incubated with M. avium subsp. paratuberculosis showed greater expression of IL-10 and GM-CSF (all time points) and IL-8 (72 h) and less expression of IL-12 (72 h), IFN-{gamma} (6 h), and TNF-{alpha} (6 h). When cytokine expression by macrophages incubated with M. avium subsp. paratuberculosis was compared to those of macrophages incubated with M. avium subsp. avium, M. avium subsp. paratuberculosis-infected cells showed greater expression of IL-10 (6 and 24 h) and less expression of TNF-{alpha} (6 h). Therefore, the combination of inherent resistance to intracellular degradation and suppression of macrophage activation through oversecretion of IL-10 may contribute to the virulence of M. avium subsp. paratuberculosis in cattle.

* Corresponding author. Mailing address: Department of Veterinary Pathobiology, University of Minnesota, 1971 Commonwealth Ave., St. Paul, MN 55108. Phone: (612) 625-9242. Fax: (612) 625-5203. E-mail: weiss005{at}tc.umn.edu.

Editor: S. H. E. Kaufmann

Infection and Immunity, October 2002, p. 5556-5561, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5556-5561.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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