Estradiol-induced immune suppression via prostaglandin E2 during
parturition in bovine leukemia virus-infected cattle
Abstract
Immune suppression during pregnancy and parturition is considered a risk
factor that is related to the progression of bovine chronic diseases,
such as bovine leukosis, which are caused by bovine leukemia virus
(BLV). Our previous studies have demonstrated that prostaglandin E2
(PGE2) suppresses BLV-specific Th1 responses and contributes to the
disease progression during BLV infection. Although PGE2 reportedly plays
important roles in the induction of parturition, PGE2 involvement in
immune suppression during parturition is unknown. To investigate its
involvement, we analyzed PGE2 kinetics and Th1 responses in BLV-infected
pregnant cattle. PGE2 concentrations in sera were increased, whereas
IFN-γ responses were decreased before delivery. PGE2 is known to
suppress Th1 immune responses in cattle. Thus, these data suggest that
PGE2 upregulation inhibits Th1 responses during parturition. We also
found that estradiol was important for PGE2 induction in pregnant
cattle. In vitro analyses indicated that estradiol suppressed IFN-γ
production, at least in part, via PGE2/EP4 signaling. In vivo analyses
showed that estradiol administration significantly influenced the
induction of PGE2 production and impaired Th1 responses. Our data
suggest that estradiol-induced PGE2 is involved in the suppression of
Th1 responses during pregnancy and parturition in cattle, which could
contribute to the progression of BLV infection.