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Vet. Res.
Volume 38, Number 4, July-August 2007
Page(s) 547 - 564
Published online 30 May 2007
How to cite this article Vet. Res. (2007) 547-564
Vet. Res. 38 (2007) 547-564
DOI: 10.1051/vetres:2007015

Splenic immune responses during canine visceral leishmaniasis

Dalit Strauss-Ayalia, b, c, Gad Banetha and Charles L. Jaffec

a  School of Veterinary Medicine, Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel
b  Present address: Department of Cell Biology and Molecular Genetics, 1105 Microbiology Bldg., University of Maryland, College Park, MD 20742, USA
c  The Kuvin Center for the Study of Tropical and Infectious Diseases, Hebrew University - Hadassah Medical School, Jerusalem, Israel

(Received 4 October 2006; accepted 9 January 2007; published online 30 May 2007)

Abstract - Dogs are the main reservoir host for zoonotic visceral leishmaniasis caused by Leishmania infantum. In this study we investigated the immune response in spleens of L. infantum-infected dogs by measuring the mRNA expression levels for a wide panel of cytokines, transcription factors and chemokines. mRNA levels and parasite load were followed during 7 months of experimental infection and 14 months post-treatment, and were compared to naturally-infected (NI) dogs. Similarly, serum anti-Leishmania IgG and IgG subclass levels were measured during experimental infection. An increase in IFN-$\gamma$, T-bet, IP-10 and RANTES was found in the experimentally and NI dogs, implicating a substantial type-1 immune response during canine visceral leishmaniasis. IL-4, a type-2 associated cytokine, increased as early as one month after experimental infection, while IL-5 was high at later stages. Interestingly, the expression levels of the Treg-associated cytokines, IL-10 and TGF-$\beta$, did not change during the infection. Total anti-Leishmania IgG and IgG subclasses increased during the experimental infection. However, no association with specific cytokine patterns was observed. Parasite load in the spleens increased as early as one month post-infection and remained high until treatment. The load was higher in the polysymptomatic NI dogs than in the experimentally-infected dogs. This study indicates that both type-1 and type-2 immune responses occur in the spleen during canine L. infantum infection, and suggests that the early elevation of IL-4 might have a role in the persistence of parasites in the presence of high IFN-$\gamma$ expression.

Key words: canine visceral leishmaniasis / IFN-$\gamma$ / IL-4 / T-bet / IP-10

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© INRA, EDP Sciences 2007