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Infection and Immunity, May 2002, p. 2559-2565, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2559-2565.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Inhibition of Apoptosis by Gamma Interferon in Cells and Mice Infected with Chlamydia muridarum (the Mouse Pneumonitis Strain of Chlamydia trachomatis)

Jean-Luc Perfettini,¹ Toni Darville,² Alice Dautry-Varsat,³ Roger G. Rank,² and David M. Ojcius^1*

Unité de Biologie Moléculaire du Gène, INSERM U277, Université Paris 7,¹ Unité de Biologie des Interactions Cellulaires, URA CNRS 1960, Institut Pasteur, 75724 Paris Cedex 15, France,³ Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205²

Received 16 July 2001/ Returned for modification 31 August 2001/ Accepted 25 January 2002

The effect of gamma interferon (IFN-) on apoptosis due to infection by Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis) was studied in epithelial cells in culture and in the genital tracts of mice. IFN- concentrations that induce the formation of aberrant, persistent chlamydiae inhibit apoptosis due to C. muridarum infection. In cells treated with an IFN- concentration that leads to the development of a heterogenous population of normal and aberrant Chlamydia vacuoles, apoptosis was inhibited preferentially in cells that contained the aberrant vacuoles. The inhibitory effect of IFN- appears to be due in part to expression of host cell indoleamine 2,3-dioxygenase activity, since inhibition of apoptosis could be partially reversed through coincubation with exogenous tryptophan. Apoptotic cells were observed in the genital tracts of wild-type mice infected with C. muridarum, and a significantly larger number of apoptotic cells was detected in infected IFN--deficient mice. These results suggest that IFN- may contribute to pathogenesis of persistent Chlamydia infections in vivo by preventing apoptosis of infected cells.

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* Corresponding author. Mailing address: Unité de Biologie Moléculaire du Gène, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: (33) 1 40 61 36 34. Fax: (33) 1 45 68 85 48. E-mail: ojcius{at}pasteur.fr.

Editor: S. H. E. Kaufmann

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Infection and Immunity, May 2002, p. 2559-2565, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2559-2565.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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