International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

THURSDAY OCTOBER 21

9.15am – 9.30am

SEX DEPENDENT SUSCEPTIBILITY PATTERN TO LISTERIA MONOCYTOGENES INFECTION IS MEDIATED BY DIFFERENTIAL IL-10 PRODUCTION

Kalaydjiev S1, Pasche B2, Franz TJ1, Kremmer E3, Gailus-Durner V4, Fuchs H4, Hrabe de Angelis M1, Busch DH1, Lengeling A2

1 Institute for Medical Microbiology, Immunology, and HygieneTechnical University Munich, Munich, Germany, 2 Junior Research Group Infection Genetics, German Research Centre for Biotechnology (GBF), Braunschweig, Germany, 3 Institute of Molecular Immunology, GSF - National Research Center for Environment and Health, Munich, Germany, 4 German Mouse Clinic, Institute of Experimental Genetics, GSF - National Research Center for Environment and Health, Neuherberg, Germany

Infectious diseases are a major cause of morbidity and mortality worldwide. It is well established that the sex of a host can significantly affect susceptibility to infection. A number of reports have shown that patients of one sex are more likely to get an infectious disease, and gender is often referred to as risk factor for the severity and outcome of an illness. The underlying molecular mechanisms of this predisposition are largely unknown.

Listeria monocytogenes (L.m.) is an intracellular Gram-positive bacterium that causes diseases in immunocompromised individuals and pregnant women, often with deleterious consequences for the fetus. It is also one of the most widely used pathogens in experimental mouse studies that provided the basis for establishing major paradigms in contemporary immunology.

Although most mouse infection models demonstrate higher resistance in females, we made the unexpected observation that female mice are significantly more susceptible to L.m. infection compared to their male littermates. Surprisingly, increased severity of infection in females is correlated with elevated IL-10 plasma levels. Experiments using IL-10-knockout mice, in which no differences between the susceptibility of males and females to L.m. infection could be detected, confirmed the crucial role of this immunosuppressive cytokine for the outcome of disease.

Our findings might be of substantial clinical importance, since similar sex differences in infection with L.m. and other intracellular pathogens have been reported in humans.

This work is supported by the National Genome Research Network NGFN (01GR0102-KB-P5T0513) and by the EU project EUMORPHIA (QLG2-CT-2002-00930).

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