Type I interferons (IFN-I) are critical for antiviral immunity; however, chronic IFN-I signaling is associated with hyperimmune activation and disease progression in persistent infections. We demonstrated in mice that blockade of IFN-I signaling diminished chronic immune activation and immune suppression, restored lymphoid tissue architecture, and increased immune parameters associated with control of virus replication, ultimately facilitating clearance of the persistent infection. The accelerated control of persistent infection induced by blocking IFN-I signaling required CD4 T cells and was associated with enhanced IFN-γ production. Thus, we demonstrated that interfering with chronic IFN-I signaling during persistent infection redirects the immune environment to enable control of infection.
"Some studies suggest that local cytokine exposure during infection might play a polarizing role on naive CD4 + T cells toward a certain T helper (Th) cell subset upon subsequent coinfection with a secondary pathogen (Perona-Wright et al., 2010). Other studies suggest that elevated cytokine concentrations might play a role in propagating the exhaustion that occurs during chronic infections (Teijaro et al., 2013; Wilson et al., 2013). Immune stimulatory therapies are being increasingly successfully applied as cancer treatments. "
"Important functions of this family of cytokines include inducing an antimicrobial state, moderating innate immunity, and activating adaptive immunity. Although IFN-Is have generally been thought to be beneficial to the immune response against microbial infections, recent research has shown that IFN-I signaling may be detrimental in several pathogenic infections (Davidson et al., 2014; Harris et al., 2010; Mayer-Barber et al., 2014; Teijaro et al., 2013; Teles et al., 2013; Wilson et al., 2013). Further, persistent viral infections such as HIV, SIV, and HCV are characterized by high interferon signatures suggesting that high levels of IFN-I signaling may play a role in disease pathogenesis (Bolen et al., 2013; Hardy et al., 2013; Sedaghat et al., 2008; Stylianou et al., 2000). "
"Thus modest improvements in T cell function may be insufficient to improve viral control. Studies of chronic LCMV infections have shown that, paradoxically , the number one enemy of many viral infections, IFN-I, enhances CD4 T cell exhaustion and promotes viral persistence, possibly as a tactic for avoiding immunopathology (Teijaro et al., 2013; Wilson et al., 2013). "
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.