The Role of IL-10 in Regulating Immunity to Persistent Viral Infections

Abstract

The immune system has evolved multipronged responses that are critical to effectively defend the body from invading pathogens and to clear infection. However, the same weapons employed to eradicate infection can have caustic effects on normal bystander cells. Therefore, tight regulation is vital and the host must balance engendering correct and sufficient immune responses to pathogens while limiting errant and excessive immunopathology. To accomplish this task a complex network of positive and negative immune signals are delivered that in most instances successfully eliminate pathogen. However, in response to some viral infections, immune function is rapidly suppressed leading to viral persistence. Immune suppression is a critical obstacle to the control of many persistent virus infections such as HIV, hepatitis C and hepatitis B virus, which together affect more than 500 million individuals worldwide. Thus, the ability to therapeutically enhance immunity is a potentially powerful approach to resolve persistent infections. The host derived cytokine IL-10 is a key player in the establishment and perpetuation of viral persistence. This chapter discusses the role of IL-10 in viral persistence and explores the exciting prospect of therapeutically blocking IL-10 to increase antiviral immunity and vaccine efficacy.

Cytokine profiles of dendritic cells (DCs) during infection with bovine leukaemia virus (BLV)

“…It has been shown that IL-10 can induce DCs apoptosis in vitro and substantially reduces the ability to effectively present antigens by suppression of DCs differentiation and maturation (Pinzon-Charry et al 2005). Suppression of antigen presentation in DCs is a keystone of immunotolerance; however this property is often utilized by viruses to limit the immune response during infection (Wilson and Brooks 2011).…”

“…As a result, impairment of DCs maturation with dominance of immature phenotype, responsible for immunological tolerance, over mature phenotype engaged in antigen presentation and control of immunological reaction, was observed. It has also been shown that intensified IL-10 expression suppresses production of proinflammatory cytokines IL-12 and IFN-γ, which are crucial for induction of the Th1 response (Wilson and Brooks 2011).…”

Kupffer cell in the immune activation and tolerance toward HBV/HCV infection

“…34 A higher level of IL-10 mRNA expression was detected in monocytes from chronic HCV patients. 35 Studies have shown that HCV core protein induces KCs to secrete IL-10, in order to suppress secretion of pro-inflammatory factors. 36 IL-10 can also down-regulate major histocompatibility complex (MHC) class II molecules and costimulatory molecules, so interaction between KCs and NK cells, as well as their antigen-presenting function, can be suppressed.…”

“…36 IL-10 can also down-regulate major histocompatibility complex (MHC) class II molecules and costimulatory molecules, so interaction between KCs and NK cells, as well as their antigen-presenting function, can be suppressed. 35 IL-10 can not only terminate the immune response of T cells, but can also suppress T cells' immune activities toward the virus. 37 The direct influence of IL-10 on antigen-presenting cells can reduce the expression of the stimulating factor, inhibiting the secretion of cytokines and eventually making it hard to activate T cells.…”

“…37 The direct influence of IL-10 on antigen-presenting cells can reduce the expression of the stimulating factor, inhibiting the secretion of cytokines and eventually making it hard to activate T cells. 35 In an HBV-infected mouse model, when KCs were removed, the production of IL-10 and IFN-γ decreased sharply. Researchers co-cultured KCs and CD4+T cells, and found that KCs from mice infected with HBV could induce CD4+T cells to produce IL-10 and generate Tr1-like cells.…”