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Review
. 2017 Nov 13;31(17):2317-2330.
doi: 10.1097/QAD.0000000000001645.

Natural killer cells in HIV-1 infection and therapy

Joanna Mikulak  1 , Ferdinando Oriolo, Elisa Zaghi, Clara Di Vito, Domenico Mavilio
Affiliations
Review

Natural killer cells in HIV-1 infection and therapy

Joanna Mikulak et al. AIDS. .

Abstract

: Natural killer (NK) cells are important effectors of innate immunity playing a key role in the eradication and clearance of viral infections. Over the recent years, several studies have shown that HIV-1 pathologically changes NK cell homeostasis and hampers their antiviral effector functions. Moreover, high levels of chronic HIV-1 viremia markedly impair those NK cell regulatory features that normally regulate the cross talks between innate and adaptive immune responses. These pathogenic events take place early in the infection and are associated with a pathologic redistribution of NK cell subsets that includes the expansion of anergic CD56/CD16 NK cells with an aberrant repertoire of activating and inhibitory receptors. Nevertheless, the presence of specific haplotypes for NK cell receptors and the engagement of NK cell antibody-dependent cell cytotocity have been reported to control HIV-1 infection. This dichotomy can be extremely useful to both predict the clinical outcome of the infection and to develop alternative antiviral pharmacological approaches. Indeed, the administration of antiretroviral therapy in HIV-1-infected patients restores NK cell phenotype and functions to normal levels. Thus, antiretroviral therapy can help to develop NK cell-directed therapeutic strategies that include the use of broadly neutralizing antibodies and toll-like receptor agonists. The present review discusses how our current knowledge of NK cell pathophysiology in HIV-1 infection is being translated both in experimental and clinical trials aimed at controlling the infection and disease.

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Conflict of interest statement

Conflict of Interest

There are no conflicts of interest

Figures

Figure 1
Figure 1. Impact of HIV-1 on NK cell homeostasis and functions
Since from the early stages of HIV-1 infection when tissue-resident antigen presenting cells (APCs) such as immature Dendritic Cells (iDCs) uptake the virus, the defective crosstalk between NK cells and DCs lead to an aberrant maturation and to the infection of these APCs (1). Once migrated to secondary lymphoid organs, these aberrant mature DCs (mDCs) contribute to infect autologous CD4+ T cells instead of ensuring an optimal activation and priming of adaptive immune responses (2). High levels of HIV-1 replication also markedly affects NK cell phenotype and function by inducing the expansion of an anergic subset that lack bot CD56 and Siglec-7 and that is highly impaired in killing autologous and viral infected CD4+ T cells, in the clearance of opportunistic infections and tumors and in performing antibody dependent cell cytotoxicity (ADCC) (3). This aberrant and highly pathogenic vicious loop is completely reversible following the administration of antiretroviral therapy that can restore NK cell homeostasis and anti-viral functions, thus making them an ideal cellular tool to follow-up disease progression and treatment efficacy as well as to develop alternative curative strategies to clear the infection.
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