ABSTRACT
Type I IFN signaling is a central pathway that provides critical innate protection from viral and bacterial infection and can have regulatory outcomes in inflammatory settings. We determined previously that OPCs contained in the dietary supplement APP enhanced responses to type I IFN in vitro. Here, we confirm that OPCs from two different sources significantly increased pSTAT1, whereas a monomeric form of procyanidin did not. We hypothesized that similar responses could be induced in vivo following ingestion of APP. Ingestion of APP before injection of polyI:C enhanced in vivo responses to type I IFNs in mice. When human subjects ingested APP, enhanced responses to type I IFN and enhanced pSTAT1 ex vivo were detected, whereas ingestion of RES, a monomeric polyphenol, induced minimal such changes. Polyphenols are best known for induction of anti-inflammatory and antioxidant responses; however, our findings suggest a unique, nonantioxidant aspect of OPCs that is broadly applicable to many disease settings. The capacity of oral OPCs to enhance type I IFN signaling in vivo can augment innate protection and may, in part, contribute to the noted anti-inflammatory outcome of ingestion of OPCs from many sources.
Subject(s)
Biflavonoids/administration & dosage , Catechin/administration & dosage , Chlorogenic Acid/administration & dosage , Flavonoids/administration & dosage , Immunity, Innate/drug effects , Interferon Type I/immunology , Proanthocyanidins/administration & dosage , Tannins/administration & dosage , Administration, Oral , Animals , Double-Blind Method , Female , Humans , Male , Mice , Mice, Inbred BALB CABSTRACT
Oligomeric procyanidins (OPCs) have been shown to have antiviral and immunostimulatory effects. OPCs isolated from non-ripe apple peel were tested for capacity to reduce dengue virus (DENV) titers. Similar to published accounts, OPCs exhibited direct antiviral activity. The possibility of enhanced innate immune protection was also tested by measuring and characterizing gene and protein expression induced by OPCs during DENV infection. Treatment of DENV-infected human PBMCs with OPCs decreased viral titers and affected the expression of critical innate antiviral immune products. OPCs enhanced expression of MXI and IFNB transcripts in high MOI DENV infected PBMC cultures, and phosphorylation of STAT2 in response to recombinant type I IFN (IFN I). During low MOI infection, addition of OPCs increased expression of STAT1 transcripts, MHC I and TNFα protein production. Thus, OPCs exhibited innate immune stimulation of cells in DENV-infected cultures and uninfected cells treated with IFN I. While OPCs from a number of sources are known to exhibit antiviral effects, their mechanisms are not precisely defined. The capacity of OPCs to increase sensitivity to IFN I could be broadly applicable to many viral infections and two separate antiviral mechanisms suggest that OPCs may represent a novel, robust antiviral therapy.
