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Infection and Immunity, May 2002, p. 2288-2296, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2288-2296.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Gender Is a Major Determinant of the Clinical Evolution and Immune Response in Hamsters Infected with Leishmania spp.

Bruno L. Travi,1* Yaneth Osorio,1 Peter C. Melby,2,3 Bysani Chandrasekar,3 Lourdes Arteaga,1 and Nancy G. Saravia1

Centro Internacional de Entrenamiento e Investigaciones Medicas-CIDEIM, Cali, Colombia,1 Medical Service, Department of Veterans Affairs Medical Center, South Texas Veterans Health Care System,2 Department of Medicine, The University of Texas Health Science Center, San Antonio, Texas3

Received 4 October 2001/ Returned for modification 21 December 2001/ Accepted 31 January 2002

In regions where leishmaniasis is endemic, clinical disease is usually reported more frequently among males than females. This difference could be due to disparate risks of exposure of males and females, but gender-related differences in the host response to infection may also play a role. Experimental studies of the influence of gender on Leishmania infection have not included parasites of the subgenus Viannia, which is the most common cause of cutaneous leishmaniasis in the Americas. Mice are not readily susceptible to infection by Leishmania (Viannia) spp., but cutaneous infection of hamsters with L. (V.) panamensis or L. (V.) guyanensis resulted in chronic lesions typical of the human disease caused by these parasites. Strikingly, infection of male hamsters resulted in significantly greater lesion size and severity, an increased rate of dissemination to distant cutaneous sites, and a greater parasite burden in the draining lymph node than infection in female animals. Two lines of evidence indicated this gender-related difference in disease evolution was determined at least in part by the sex hormone status of the animal. First, prepubertal male animals had smaller and/or less severe cutaneous lesions than adult male animals. Second, infection of testosterone-treated female animals resulted in significantly larger lesions than in untreated female animals. The increased severity of disease in male compared to female animals was associated with significantly greater intralesional expression of interleukin-4 (IL-4) (P = 0.04), IL-10 (P = 0.04), and transforming growth factor ß (TGF-ß) (P < 0.001), cytokines known to promote disease in experimental leishmaniasis. There was a direct correlation between the expression of TGF-ß mRNA and lesion size (Spearman's correlation coefficient = 0.873; P < 0.001). These findings demonstrate an inherent risk of increased disease severity in male animals, which is associated with a more permissive immune response.

* Corresponding author. Mailing address: CIDEIM, AA5390, Cali, Colombia. Phone: 57-2-668-2160. Fax: 57-2-667-2989. E-mail: travib{at}cideim.org.co.

Editor: W. A. Petri, Jr.

Infection and Immunity, May 2002, p. 2288-2296, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2288-2296.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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