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Infection and Immunity, September 2005, p. 5827-5834, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5827-5834.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Toward a Novel Experimental Model of Infection To Study American Cutaneous Leishmaniasis Caused by Leishmania braziliensis

Tatiana R. de Moura,1,{dagger} Fernanda O. Novais,1,{dagger} Fabiano Oliveira,1 Jorge Clarêncio,1 Almério Noronha,1 Aldina Barral,1,2 Claudia Brodskyn,1,3 and Camila I. de Oliveira1*

Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Salvador, BA 40295-001,1 Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Praça XV de Novembro S/N, Largo do Terreiro de Jesus, Salvador, BA 40025-010,2 Departamento de Biointeração, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Av. Reitor Miguel Calmon, S/N, Salvador, BA 40110-160, Brazil3

Received 28 January 2005/ Returned for modification 8 March 2005/ Accepted 25 March 2005

Leishmania spp. cause a broad spectrum of diseases collectively known as leishmaniasis. Leishmania braziliensis is the main etiological agent of American cutaneous leishmaniasis (ACL) and mucocutaneous leishmaniasis. In the present study, we have developed an experimental model of infection that closely resembles ACL caused by L. braziliensis. In order to do so, BALB/c mice were infected in the ear dermis with 105 parasites and distinct aspects of the infection were evaluated. Following inoculation, parasite expansion in the ear dermis was accompanied by the development of an ulcerated dermal lesion which healed spontaneously, as seen by the presence of a scar. Histological analysis of infected ears showed the presence of a mixed inflammatory infiltrate consisting of both mononuclear and polymorphonuclear cells. In draining lymph nodes, parasite replication was detected throughout the infection. In vitro restimulation of draining lymph node cells followed by intracellular staining showed an up-regulation in the production of gamma interferon (IFN-{gamma}) and in the frequency of IFN-{gamma}-secreting CD4+ and CD8+ T cells. Reverse transcription-PCR of ears and draining lymph node cells showed the expression of CC chemokines. The dermal model of infection with L. braziliensis herein is able to reproduce aspects of the natural infection, such as the presence of an ulcerated lesion, parasite dissemination to lymphoid areas, and the development of a Th1-type immune response. These results indicate that this model shall be useful to address questions related to the concomitant immunity to reinfection and parasite persistence leading to mucocutaneous leishmaniasis.

* Corresponding author. Mailing address: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Salvador, BA 40295-001, Brazil. Phone: 55-71-356 8785, ext. 211. Fax: 55-71-356 8785, ext. 261. E-mail: camila{at}cpqgm.fiocruz.br.

Editor: W. A. Petri, Jr.

{dagger} T. R. de Moura and F. O. Novais contributed equally to this work.

Infection and Immunity, September 2005, p. 5827-5834, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5827-5834.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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