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  • Review Article
  • Published:

DCs and NK cells: critical effectors in the immune response to HIV-1

Nature Reviews Immunology volume 11, pages 176–186 (2011)Cite this article

Subjects

Key Points

  • Dendritic cells (DCs) use distinct cell-specific receptors for binding to HIV that differentially affect both the fate of the virus and the subsequent effect of the virus on DCs.

  • The ability of conventional DCs (cDCs) to respond to HIV-1 is dysregulated. This may be due to a lack of Toll-like receptor (TLR)-mediated recognition of the virus; the modulation of internal signalling in cDCs by HIV-1 (such as through C-type lectins); or an indirect effect mediated by factors that are produced in the environment during HIV-1 infection. Such dysregulation may impede the ability of cDCs to stimulate adaptive immune responses to HIV-1.

  • Plasmacytoid DCs (pDCs) respond to HIV-1 through TLR7-mediated recognition of viral genomic RNA and produce type I interferons, which can limit viral replication but also contribute to bystander T cell death. pDCs further contribute to deleterious immunopathology during HIV-1 infection by secreting chemokines that attract uninfected T cells to the site of infection, and by inducing regulatory T cells, which can suppress the immune response to HIV-1.

  • Natural killer (NK) cells play an important immunoregulatory role in viral infection, including during HIV-1 infection, by secreting cytokines and by 'editing' DC function.

  • NK cells can also directly recognize HIV-1-infected cells using an array of different receptors, including activating receptors, killer cell immunoglobulin-like receptors and the CD16 receptor, which mediates antibody-dependent cell cytotoxicity.

  • Crosstalk between NK cells and DCs is crucial for optimizing the maturation of DCs and enhancing the ability of DCs to prime adaptive immune responses. However, HIV-1 infection interferes with this crosstalk.

Abstract

Dendritic cells (DCs) and natural killer (NK) cells have central roles in antiviral immunity by shaping the quality of the adaptive immune response to viruses and by mediating direct antiviral activity. HIV-1 infection is characterized by a severe dysregulation of the antiviral immune response that starts during early infection. This Review describes recent insights into how HIV-1 infection affects DC and NK cell function, and the roles of these innate immune cells in HIV-1 pathogenesis. The importance of understanding DC and NK cell crosstalk during HIV infection for the development of effective antiviral strategies is also discussed.

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Figure 1: cDCs and pDCs during HIV infection.
Figure 2: NK cell-mediated recognition of HIV-1-infected cells.
Figure 3: DC–NK cell crosstalk.

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Acknowledgements

This work was supported by grants from the US National Institutes of Health (to N.B. and M.A.), the Doris Duke Charitable Foundation (to M.A.), the Bill & Melinda Gates Foundation (to N.B. and M.A.) and the Phillip T. and Susan M. Ragon Foundation (to M.A. and L.F.).

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  1. Marcus Altfeld, Lena Fadda, Davor Frleta and Nina Bhardwaj: All authors contributed equally to this work.

Authors and Affiliations

  1. Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Charlestown, 02129, Massachusetts, USA

    Marcus Altfeld & Lena Fadda

  2. New York University Cancer Institute, NYU Langone Medical Center, New York, 10016, New York, USA

    Davor Frleta & Nina Bhardwaj

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Correspondence to Marcus Altfeld or Nina Bhardwaj.

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Nina Bhardwaj is an inventor on patents related to the use of dendritic cells as immunomodulators.

Glossary

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Granzyme A

A member of a family of serine proteinases that are found, primarily, in the cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells. Granzymes enter target cells through perforin pores, then cleave and activate intracellular caspases to initiate target cell apoptosis.

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Altfeld, M., Fadda, L., Frleta, D. et al. DCs and NK cells: critical effectors in the immune response to HIV-1. Nat Rev Immunol 11, 176–186 (2011). https://doi.org/10.1038/nri2935

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