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Infection and Immunity, August 2000, p. 4470-4476, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Adaptive Immunity against Listeria monocytogenes in the Absence of Type I Tumor Necrosis Factor Receptor p55

Douglas W. White,1 Vladimir P. Badovinac,2 Xin Fan,3 and John T. Harty1,2,*

Interdisciplinary Graduate Program in Immunology1 and Department of Microbiology,2 University of Iowa, Iowa City, Iowa 52242, and Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 191043

Received 23 November 1999/Returned for modification 14 February 2000/Accepted 2 May 2000

Tumor necrosis factor (TNF) and the type I TNF receptor (TNFRI), p55, are critical for resistance against primary infections with the intracellular bacterial pathogen Listeria monocytogenes. Importantly, however, susceptibility to primary listeriosis in cytokine-deficient mice does not preclude the development or expression of effective adaptive immunity against virulent L. monocytogenes. We used TNFRI-/- mice to study adaptive antilisterial immunity in the absence of interactions between TNF and TNFRI. Our experiments indicate that TNFRI-/- mice survive and clear high-dose challenges with an attenuated strain of L. monocytogenes that is incapable of cell-to-cell spread. Furthermore, TNFRI-/- mice immunized with attenuated L. monocytogenes go on to develop potent adaptive immunity to subsequent high-dose challenges with virulent L. monocytogenes. Interestingly, CD8+ T-cell depletion in vivo inhibits immunity to L. monocytogenes in the spleen but not in the liver of TNFRI-/- mice. The adaptive immune response in these animals is characterized by activation of listeriolysin O-specific CD8+ T cells, which are capable of transferring antilisterial immunity to naive wild-type C57BL/6 host mice. These experiments demonstrate the development and expression of potent CD8+ T-cell-mediated antilisterial immunity in the absence of TNFRI.

* Corresponding author. Mailing address: 3-512 Bowen Science Building, Department of Microbiology, University of Iowa, Iowa City, IA 52242. Phone: (319) 335-9720. Fax: (319) 335-9006. E-mail: john-harty{at}uiowa.edu.

Infection and Immunity, August 2000, p. 4470-4476, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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