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Infection and Immunity, September 2005, p. 6085-6090, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.6085-6090.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Arginase I Induction during Leishmania major Infection Mediates the Development of Disease

Virginia Iniesta,1 Jesualdo Carcelén,1 Isabel Molano,1 Pablo M. V. Peixoto,2 Eloy Redondo,3 Pilar Parra,3 Marina Mangas,1 Isabel Monroy,1 Maria Luisa Campo,2 Carlos Gómez Nieto,1 and Inés Corraliza2*

Unidad de Parasitología y Enfermedades Parasitarias,1 Departamento de Bioquímica y Biología Molecular,2 Unidad de Histología y Anatomía Patológica, Facultad de Veterinaria, Universidad de Extremadura, Cáceres, Spain3

Received 20 January 2005/ Returned for modification 8 March 2005/ Accepted 9 May 2005

In a previous work, we demonstrated that the induction of arginase I favored the replication of Leishmania inside macrophages. Now we have analyzed the differential expression of this enzyme in the mouse model of L. major infection. Ours results show that arginase I is induced in both susceptible and resistant mice during the development of the disease. However, in BALB/c-infected tissues, the induction of this protein parallels the time of infection, while in C57BL/6 mice, the enzyme is upregulated only during footpad swelling. The induction of the host arginase in both strains is mediated by the balance between interleukin-4 (IL-4) and IL-12 and opposite to nitric oxide synthase II expression. Moreover, inhibition of arginase reduces the number of parasites and delays disease outcome in BALB/c mice, while treatment with L-ornithine increases the susceptibility of C57BL/6 mice. Therefore, arginase I induction could be considered a marker of disease in leishmaniasis.

* Corresponding author. Mailing address: Facultad de Veterinaria, Universidad de Extremadura. Avda. de la Universidad s/n, Cáceres 10071, Spain. Phone: (927) 257000, ext. 1335. Fax: (927) 257161. E-mail: corragen{at}unex.es.

Editor: J. F. Urban, Jr.

Infection and Immunity, September 2005, p. 6085-6090, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.6085-6090.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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