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. 2011:677:431-47.
doi: 10.1007/978-1-60761-869-0_27.

Immunosuppressive mechanisms during viral infectious diseases

Ghanashyam Sarikonda  1 , Matthias G von Herrath
Affiliations

Immunosuppressive mechanisms during viral infectious diseases

Ghanashyam Sarikonda et al. Methods Mol Biol. 2011.

Abstract

For a virus to establish persistence in the host, it has to exploit the host immune system such that the active T-cell responses against the virus are curbed. On the other hand, the goal of the immune system is to clear the virus, following which the immune responses need to be downregulated, by a process known as immunoregulation. There are multiple known immunoregulatory mechanisms that appear to play a role in persistent viral infections. In the recent past, IL-10 and PD-1 have been identified to be playing a significant role in the regulation of antiviral immune responses. The evidence that viruses can escape immunologic attack by taking advantage of the host's immune system is found in LCMV infection of mice and in humans persistently infected with HIV and HCV. The recent observation that the functionally inactive T-cells during chronic viral infections can be made to regain their cytokine secretion and cytolytic abilities is very encouraging. Thus, it would be likely that neutralization negative immune regulation during persistent viral infection would result in the preservation of effector T-cell responses against the virus, thereby resulting in the elimination of the persistent infection.

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Figures

Fig. 1.
Fig. 1.
Immune regulation during persistent viral infection. In an acute infection (left), when a virus infects a normal cell, it is phagocytosed by antigen presenting cell (APC) (dendritic cell [DC] or MΦ). The APCs efficiently present the viral antigens to CD4 and CD8 cells, which either release proinflammatory cytokines (TNF-α, IFN-γ) or upregulate perforin, which kills the infected cells, ultimately leading to the elimination of the virus. However, in persistent infection (right), due to a number of reasons, including miRNAs and molecular mimicry, viruses evade immune recognition. Thus, the CD4 and CD8 cells are not sufficiently activated and the virus avoids immune-mediated elimination. On the other hand, APCs (MΦ and DCs), upon TLR2 activation, upregulate IL-10; IL-10 exhibits significant immunosuppressive effects leading to the inactivation of CD4 and CD8 T-cells. Further, activated T-cells also upregulate CTLA-4 that prevents costimulation, thereby leading to inactivation. And, finally, virus antigen-specific T-cells also upregulate PD-1 which, upon engagement with its ligand PD-L1, signals the death of that T-cell. These events, help to avoid immune response mediated host tissue damage but at the cost of establishing viral persistence.
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