Differences in IFNβ secretion upon Rab1 inactivation in cells exposed to distinct innate immune stimuli

摘要

Type I interferons(IFNs)are secretory cytokines with protective roles against viral infection.Most studies have focused on the signaling pathways that regulate the transcriptional activation of type I IFNs;however,little is known about the secretory mechanism of these cytokines,except for information obtained from a few studies reporting the secretion polarity of IFNβin epithelial cells.1,2,3,4 Here,we investigate the role of Rab1,a small GTPase of the Rab family,in IFNβsecretion.We show that Rab1 inactivation blocked the secretion of IFNβfrom human embryonic kidney 293T(HEK293T)cells transfected with IFNβ-inducing molecules(TRIF,MAVS,and TBK1)but not from cells stimulated with RNA ligands(Sendai virus)(SeV)or polyinosinic:polycytidylic acid(poly(I:C)).Despite the differential effects of Rab1 inactivation and regardless of the triggering stimuli,IFNβsecretion was inhibited by brefeldin A(BFA),a fungal metabolite that inhibits ER-to-Golgi transport.In addition,a proportion of endogenous 3×Flag-tagged IFNβcolocalized with the cis-Golgi marker GM130 within SeV-infected cells.Our results indicate that IFNβsecretion generally requires the conventional ER-Golgi pathway while showing differential responses to Rab1 inactivation in cells exposed to distinct innate immune stimuli.