Польза от хронических инфекций

Chronic infections with viruses or parasites: breaking bad to make good

Summary

Eukaryotic forms of life have been continually invaded by microbes and larger multicellular parasites, such as helminths. Over a billion years ago bacterial endosymbionts permanently colonized eukaryotic cells leading to recognized organelles with a distinct genetic lineage, such as mitochondria and chloroplasts. Colonization of our skin and mucosal surfaces with bacterial commensals is now known to be important for host health. However, the contribution of chronic virus and parasitic infections to immune homeostasis is being increasingly questioned. Persistent infection does not necessarily equate to exhibiting a chronic illness: healthy hosts (e.g. humans) have chronic viral and parasitic infections with no evidence of disease. Indeed, there are now examples of complex interactions between these microbes and hosts that seem to confer an advantage to the host at a particular time, suggesting that the relationship has progressed along an axis from parasitic to commensal to one of a mutualistic symbiosis. This concept is explored using examples from viruses and parasites, considering how the relationships may be not only detrimental but also beneficial to the human host.

The good (light) and bad (dark) side of chronic virus infection. Infection of tissues by viruses and subsequent chronic inflammation can lead to tissue damage, e.g. hepatitis. In chronic hepatitis C virus (HCV) infection, progression to disease is associated with the expression of the natural killer (NK) cell receptor NKp46. Many other viruses directly infect antigen-presenting cells (APCs) or have a number of molecules that can down-regulate MHC class I expression expressed by these cells; this molecule is important for viral recognition by CD8+ T cells but is also important for elimination of tumour cells. The NK cell killing of cells expressing low MHC class I is prevented by the dismantling of NK activating receptors. viral interleukin-10 (vIL-10) can transform B cells and help the virus to establish a chronic infection. This molecule is also reported to reduce autoimmunity, inflammation and tissue rejection. Chronic virus infection can promote anti-inflammatory responses, including the expansion of regulatory T (Treg) cells and, production of transforming growth factor-β (TGF-β) and is associated with a switch from interferon-γ (IFN-γ) to IL-10-producing CD4+ T cells. Viral infection is also able to reduce antigen presentation and activation of APCs, reducing CD4+ T-cell activation and inflammatory responses.

 

http://onlinelibrary.wiley.com/doi/10.1111/imm.12703/full