Arginase I induction during Leishmania major infection mediates the development of disease.
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.
Iniesta
Virginia
V
Facultad de Veterinaria, Universidad de Extremadura. Avda. de la Universidad s/n, Cáceres 10071, Spain.
Carcelén
Jesualdo
J
Molano
Isabel
I
Peixoto
Pablo M V
PM
Redondo
Eloy
E
Parra
Pilar
P
Mangas
Marina
M
Monroy
Isabel
I
Campo
Maria Luisa
ML
Nieto
Carlos Gómez
CG
Corraliza
Inés
I
D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000502:physiology; D005528:Foot; D007150:Immunohistochemistry; D007249:Inflammation / Q000201:enzymology / Q000469:parasitology; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000201:enzymology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D001119:Arginase