PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection

CINTHIA STEMPIN; CRISTINA MOTRAN; AOKI, MP; CRISTIAN FALCÓN; CERBAN F; LAURA CERVI

Oncotarget

Impact Journals

Año: 2016 vol. 7 p. 77721 - 77721

acrophage plasticity is critical for controlling inflammation during infections, such asthose produced by helminths where alternatively activated macrophages (AAM) areaccumulated in tissues. Furthermore, in different helminth infections has beendemonstrated, an increased expression of the co-inhibitory molecule programmed deathligand 2 (PD-L2) on AAM, capable of binding programmed death 1 (PD-1), which isexpressed on activated T cells. However, the role of PD-L2 during F. hepatica infectionhas not yet been explored. We observed that F. hepatica infection or F. hepatica totalextract (TE) injection up-regulated the expression of PD-L2 on peritoneal macrophages. Inaddition, the absence of PD-L2 expression correlated with an increase in susceptibility to F.hepatica infection as evidenced by a shorter survival and increased liver damage in PD-L2deficient (KO) mice. Concomitantly, a decrease in the production of the Th2 cytokines IL-4and IL-10, and an increased production of IFN-γ were