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Infection and Immunity, May 2005, p. 2621-2627, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2621-2627.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CD4+ T Cells but Not CD8+ or {gamma}{delta}+ Lymphocytes Are Required for Host Protection against Mycobacterium avium Infection and Dissemination through the Intestinal Route

Mary Petrofsky1 and Luiz E. Bermudez1,2,3*

Kuzell Institute, California Pacific Medical Center Research Institute, San Francisco, California,1 Department of Biomedical Science, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon,2 Department of Microbiology, College of Sciences, Oregon State University, Corvallis, Oregon3

Received 11 October 2004/ Returned for modification 19 November 2004/ Accepted 17 January 2005

Disseminated Mycobacterium avium infection is common in AIDS patients that do not receive anti-AIDS therapy and in patients for whom therapy fails. M. avium is commonly acquired by ingestion, and a large number of AIDS patients have M. avium in their intestinal tracts. To better understand the dynamics of the infection in patients with AIDS, we studied orally infected mice. To determine if immunocompetent mice challenged orally with M. avium can develop protection against the infection, and if so, which cell population(s) is responsible for the protection, we exposed wild-type as well as CD4–/–, CD8–/–, and {gamma}{delta}–/– knockout mice to low concentrations of M. avium strain 101 given orally, followed by treatment with azithromycin. After 1 month, the mice were challenged with kanamycin-resistant M. avium 104. Only CD4+ T cells appeared to be required for protection against the second challenge. Both CD4+ and CD8+ T cells produced comparable amounts of gamma interferon after the first exposure to the bacterium. Tumor necrosis factor alpha was elevated in CD4+ T cells but not in CD8+ T cells. Following exposure to a small inoculum of mycobacteria orally, wild-type mice did not develop disseminated infection for approximately 4 months, although viable bacteria could be observed in the mesenteric lymph nodes. The ingestion of small numbers of M. avium cells induces a protective immune response in the intestines against subsequent infection. However, the bacteria remain viable in intestinal lymph nodes and might disseminate later.

* Corresponding author. Mailing address: 105 Magruder Hall, Dept. of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331. Phone: (541) 737-6538. Fax: (541) 737-8035. E-mail: luiz.bermudez{at}oregonstate.edu.

Editor: J. D. Clements

Infection and Immunity, May 2005, p. 2621-2627, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2621-2627.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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