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Infection and Immunity, September 2005, p. 5952-5960, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5952-5960.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Sex-Dependent Susceptibility to Listeria monocytogenes Infection Is Mediated by Differential Interleukin-10 Production

Bastian Pasche,1,{dagger} Svetoslav Kalaydjiev,2,{dagger} Tobias J. Franz,2,{dagger} Elisabeth Kremmer,3 Valérie Gailus-Durner,4 Helmut Fuchs,4 Martin Hrabé de Angelis,4 Andreas Lengeling,1 and Dirk H. Busch2*

Junior Research Group Infection Genetics, Division of Microbiology, German Research Centre for Biotechnology (GBF), Mascheroder Weg 1, 38124 Braunschweig,1 Institute for Medical Microbiology, Immunology, and Hygiene, Technical University Munich, Trogerstr. 9, 81675 Munich,2 Institute of Molecular Immunology, GSF—National Research Center for Environment and Health, 81377 Munich,3 German Mouse Clinic, Institute of Experimental Genetics, GSF—National Research Center for Environment and Health, Ingolstaedter Landstrasse 1, 85764 Munich/Neuherberg, Germany4

Received 28 February 2005/ Accepted 4 April 2005

It is well documented that sex-dependent factors affect susceptibility to infection, with most mouse models demonstrating higher resistance in females. We made the unexpected observation that infection with the intracellular bacterium Listeria monocytogenes showed an opposite pattern in several commonly used inbred mouse strains: female C57BL/6J, BALB/c, C3H/HeN, and CBA/J mice were significantly more susceptible to Listeria infection. The pronounced sensitivity of females to Listeria, which was revealed by significantly higher lethality rates, correlated also with increased bacterial numbers in organ tissues (spleen and liver) and several immunological changes in peripheral blood samples. Surprisingly, increased severity of infection in females was associated with elevated interleukin-10 (IL-10) levels in plasma. Experiments using Il10 knockout mice, for which no differences between the susceptibilities of males and females to Listeria infection could be detected, confirmed the important role of this immunosuppressive cytokine for the outcome of disease. Our findings are likely to have clinical relevance, since similar sex differences with regard to infection with Listeria monocytogenes and other intracellular pathogens have been reported for humans.

* Corresponding author. Mailing address: Institute for Medical Microbiology, Immunology, and Hygiene, Technical University Munich, Trogerstr. 9, 81675 Munich, Germany. Phone: 49 89 4140 6191. Fax: 49 89 4140 4139. E-mail: dirk.busch{at}lrz.tum.de.

Editor: A. D. O'Brien

{dagger} B.P., S.K., and T.J.F. contributed equally to this work.

Infection and Immunity, September 2005, p. 5952-5960, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5952-5960.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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