IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection

Alter, G., Kavanagh, D., Rihn, S. , Luteijn, R., Brooks, D., Oldstone, M., van Lunzen, J. and Altfeld, M. (2010) IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection. Journal of Clinical Investigation, 120(6), pp. 1905-1913. (doi:10.1172/JCI40913) (PMID:20440075) (PMCID:PMC2877944)

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Abstract

Persistent levels of IL-10 play a central role in progressive immune dysfunction associated with chronic viral infections such as HIV, but the underlying mechanisms are poorly understood. Because IL-10 affects the phenotypic and functional properties of DCs, which are responsible for initiating adaptive immune responses, we investigated whether IL-10 induces changes in DC phenotype and function in the context of HIV infection. Here, we show that IL-10 treatment of immature and mature human DCs in culture induced contrasting phenotypic changes in these populations: immature DCs exhibited aberrant resistance to NK cell–mediated elimination, whereas mature DCs exhibited increased susceptibility to NKG2D-dependent NK elimination. Treatment of immature and mature DCs with HIV resulted in potent IL-10 secretion and the same phenotypic and functional changes observed in the IL-10–treated cells. Consistent with these in vitro data, LNs isolated from individuals infected with HIV exhibited aberrant accumulation of a partially “immature” DC population. Together, these data suggest that the progressive immune dysfunction observed in chronic viral infections might be caused in part by IL-10–induced reversal of DC susceptibility to NK cell–mediated elimination, resulting in the accumulation of poorly immunogenic DCs in LNs, the sites of adaptive immune response induction.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rihn, Dr Suzannah
Authors: Alter, G., Kavanagh, D., Rihn, S., Luteijn, R., Brooks, D., Oldstone, M., van Lunzen, J., and Altfeld, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Clinical Investigation
Publisher:American Society for Clinical Investigation
ISSN:0021-9738
ISSN (Online):1558-8238

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