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Review
. 2011:350:39-65.
doi: 10.1007/82_2010_96.

The role of IL-10 in regulating immunity to persistent viral infections

Affiliations
Review

The role of IL-10 in regulating immunity to persistent viral infections

Elizabeth B Wilson et al. Curr Top Microbiol Immunol. 2011.

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, which in most instances successfully eliminate the 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 viral 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.

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Figures

Figure 1
Figure 1. Effects of IL-10 on distinct cellular targets during persistent viral infections
IL-10 mediated immunosuppression in response to viral infection occurs via both direct and indirect modulation of APC function, T and B cell activity. This figure denotes some of the important functional consequences of IL-10 targeting of distinct immune subsets. Note that IL-10 likely acts on multiple other immune and non-immune cells during viral persistence and the overall influence of IL-10 is likely a summation of all these effects. Additional mechanisms of IL-10 mediated immune modulation have been described in bacterial and autoimmune models and investigating these pathways in viral persistence will be informative.
Figure 2
Figure 2. Blocking IL-10 to enhance antiviral immunity and vaccine efficacy
Overcoming IL-10-mediated immunosuppression represents an exciting strategy to enhance antiviral T cell responses both alone and in combination with other immunotherapies. Antibody blockade of IL-10 activity alone boosts T cell function and enhances control of an established persistent LCMV infection. Further, by alleviating IL-10 mediated suppression, virus-specific T cells become reactive to otherwise ineffective therapeutic vaccines facilitating markedly enhanced T cell responses and control of persistent infection. The upregulation of IL-10 during HIV and HCV infections suggests that similar strategies may also effectively enhance antiviral immunity and control infection.

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