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ORGAN-SPECIFIC IMMUNITY IN CANINE VISCERAL LEISHMANIASIS: ANALYSIS OF SYMPTOMATIC AND ASYMPTOMATIC DOGS NATURALLY INFECTED WITH LEISHMANIA CHAGASI

We characterized key leukocyte immunophenotypes in the liver and spleen of naturally infected dogs from an area in Venezuela endemic for leishmaniasis. Dogs were classified as symptomatic or asymptomatic after serologic and physical analysis. Symptomatic dogs showed a higher parasite burden in the liver and spleen than asymptomatic dogs. The livers of asymptomatic dogs showed an effective immunity with well-organized granulomas walling off parasites in an environment of central memory CD44^lo, CD45RO^hi, activated effector CD44^hi, and CD45RO^hi T cells. These granulomas also had many major histocompatibility class II+ cells and CD11c+ dendritic cells, and cells expressing CD18 and CD44. In contrast, symptomatic livers showed a non-organized and non-effective infiltrate composed of T cells and heavily parasitized Kupffer cells and a diminished expression of activation molecules. In the spleen, the immune responses of symptomatic and asymptomatic dogs were very similar. The results showed a distinct immune response against Leishmania chagasi in target organs.

Received July 29, 2003. Accepted for publication January 7, 2004.

Acknowledgments: We are grateful to Dr. Marian Ulrich for comments on the manuscript, Dr. Dilcia Brazon (Departamento de Dermatología Sanitaria de Nueva Esparta), Jose Luis García, Doris Belizario, Wilmer Galindo, and Sister Isolina Tomedes for their extraordinary support in collecting the samples and for field work, Dr. Pedro Rivas (Unidad de Cirugía Experimental, Escuela de Medicina Vargas, Caracas) for providing samples from healthy dogs, Dr. Pedro Sanchez and Patricia Rodriguez (Banco Municipal de Sangre) for help with the flow cytometry, and Richard Ramírez for technical assistance.

Financial support: This work was supported by Fondo Nacional de Ciencia, Tecnología e Innovación (FONACIT) Proyecto S1-2001000861 (Martin A. Sanchez), S1-98000041 (Felix J. Tapia), Millennium Scientific Initiative Grant 4572B, the European Commission International Cooperation with Third World Countries (INCO) Program, and the Consejo de Desarrollo Científico y Humanístico (CDCH)-Universidad Central de Venezuela (Felix J. Tapia).

^* These authors contributed equally to this paper.

Authors’ address: Martin A. Sanchez, Nilka L, Diaz, Olga Zerpa, Emilia Negron, Jacinto Convit, and Felix J. Tapia, Laboratorio de Biologia Molecular, Instituto de Biomedicina, Universidad Central de Venezuela, Apartado 4043, Caracas 1010A, Venezuela, Telephone: 58-212-862-9604, Fax 58-212-861-1258, E-mail: ftapia{at}telcel.net.ve.

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