Resumen:
(823) ROLE OF PROGRAMMED DEATH LIGAND 2 IN MACROPHAGE ACTIVATION DURING FASCIOLA HEPATICA
INFECTION
Stempin, Cinthia C; Falcon, Cristian R.; Aoki, María Del
Pilar; Motrán, Claudia C.; Cerban, Fabio M.; Cervi, Laura
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-CONICET-UNC
Helminth infections induce an increase in co-inhibitory molecule
programmed death ligand-2 (PD-L2) which is defied as a marker
for alternatively activated macrophages and is involved in the inhibition of T cell proliferation. However, it is not known how PD-L2
modulates macrophage activation, which promotes firosis in helminth infections, whereas classical activation produces deleterious
toxic metabolites. Previously we have observed that F. hepatica
infection increases PD-L2 expression in F4/80+ cells. The aim of
this study was to investigate the role of PD-L2 in the outcome of
F. hepatica infection as well as in macrophage activation during
experimental infection with the parasite. BALB/c WT and PD-L2
KO were orally infected with 8 F. hepatica metacercariae. Survival
rate was evaluated and histological changes in liver tissues were
determined by hematoxylin and eosin staining. PD-L2 KO mice
showed increased mortality during F. hepatica infection (p<0.05).
Histological analysis of infected liver from WT and PD-L2 KO mice
showed tissue damage, being greater extent in PD-L2 KO mice.
Fasciolosis, like other helminth infections, is associated with the
induction of T-cell responses polarized to the Th2 subtype. Spleen
mononuclear cells (SMC) from WT infected mice exhibited a polarized Th2 cytokine profie in response to F. hepatica antigens
while SMC from PD-L2 infected mice showed a predominant Th1
response. On the other hand, to study macrophage activation,
peritoneal cells (PC) were obtained at different time point of infection (24, 48 and 72 hs p.i) and stimulated with LPS plus INFg
or IL4 during 24 hs. Arginase activity and nitrite production were
evaluated. The results show that, PC from PD-L2 KO infected
mice exhibit reduced arginase activity and nitrite production at 24
hs p.i. Our data indicate that PD-L2 is involved in arginase/iNOS
activation in macrophages which may play a protective role during
F. hepatica infection