Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infection

Alter, Galit; Teigen, Nickolas; Davis, Benjamin T.; Addo, Marylyn M.; Suscovich, Todd J.; Waring, Michael T.; Streeck, Hendrik; Johnston, Mary N.; Staller, Kyle; Zaman, M. Tauheed; Yu, Xu G.; Lichterfeld, Mathias; Basgoz, Nesli; Rosenberg, Eric S.; Altfeld, Marcus

doi:10.1182/blood-2005-03-1100

Cited by 311 publications

(387 citation statements)

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“…In line with this, significant activation and expansion of NK cells are observed during the acute phase of HIV-1 infection, with up to 40% of peripheral lymphocytes being part of the NK cell population (6). Although the precise stimulus required to initiate this early NK cell activation during viral infections is unknown, several recent studies have indicated a critical role of TLRs in the recognition of viruses by cells of the innate immune system (36).…”

Section: Discussionmentioning

confidence: 81%

“…The perturbations observed in the NK cell compartment during chronic HIV-1 infection include the overall increased activation of NK cells, the early loss of CD3 Ϫ CD56 bright NK cells, the accumulation of anergic CD3 Ϫ CD56 Ϫ CD16 ϩ NK cells (6,10), and the impairment of their cytotoxic capacity (6,9,10,56) and cross-talk with DCs (11). The mechanisms underlying these numeric and functional NK cell perturbations observed during viremic HIV-1 infection are not understood.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms underlying these numeric and functional NK cell perturbations observed during viremic HIV-1 infection are not understood. However, suppression of HIV-1 viremia by antiretroviral therapy results in at least a partial reconstitution of NK cell numbers and function (6,9,55). Recently, it has been demonstrated that ssRNA derived from HIV-1 LTR can activate DCs via TLR7/8 (2,25).…”

Section: Discussionmentioning

confidence: 99%

“…NK cells are furthermore capable of secreting a number of cytokines and chemokines early in viral infections that are critical in the initiation of an effective adaptive immune response (5). It has been reported that significant changes occur within the NK cell compartment during HIV-1 infection (6 -9), including perturbations in the distribution and function of NK cells, accumulation of anergic NK cells (6,10), and an impairment of NK-dendritic cell (DC) 3 cross-talk (11). Furthermore, NK cells are activated in HIV-1-infected individuals more than in matched seronegative controls (12).…”

mentioning

confidence: 99%

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Single-Stranded RNA Derived from HIV-1 Serves as a Potent Activator of NK Cells

Alter

Suscovich

Teigen

et al. 2007

The Journal of Immunology

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100

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Persistent immune activation is a hallmark of chronic viremic HIV-1 infection. Activation of cells of the innate immune system, such as NK cells, occurs rapidly upon infection, and is sustained throughout the course of the disease. However, the precise underlying mechanism accounting for the persistent HIV-1-induced activation of NK cells is poorly understood. In this study, we assessed the role of uridine-rich ssRNA derived from the HIV-1 long terminal repeat (ssRNA40) on activation of NK cells via TLR7/8. Although dramatic activation of NK cells was observed following stimulation of PBMC with ssRNA40, negligible activation was observed following stimulation of purified NK cells despite their expression of TLR8 mRNA and protein. The functional activation of NK cells by this HIV-1-encoded TLR7/8 ligand could not be reconstituted with exogenous IL-12, IFN-α, or TNF-α, but was critically dependent on the direct contact of NK cells with plasmacytoid dendritic cells or CD14+ monocytes, indicating an important level of NK cell cross-talk and regulation by accessory cells during TLR-mediated activation. Coincubation of monocyte/plasmacytoid dendritic cells, NK cells, and ssRNA40 potentiated NK cell IFN-γ secretion in response to MHC-devoid target cells. Studies using NK cells derived from individuals with chronic HIV-1 infection demonstrated a reduction of NK cell responsiveness following stimulation with TLR ligands in viremic HIV-1 infection. These data demonstrate that HIV-1-derived TLR ligands can contribute to the immune activation of NK cells and may play an important role in HIV-1-associated immunopathogenesis and NK cell dysfunction observed during acute and chronic viremic HIV-1 infection.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Single-Stranded RNA Derived from HIV-1 Serves as a Potent Activator of NK Cells

Alter

Suscovich

Teigen

et al. 2007

The Journal of Immunology

Self Cite

100

View full text Add to dashboard Cite

show abstract

“…In addition, patients with IDR have low CD4 + T-cell numbers with a hyperactivated/apoptotic phenotype and an increased size of the HIV reservoir as a possible expression of incomplete virus control, while their thymic function is reduced only partially [14]. Therefore, based on these findings, it remains to be evaluated whether HIV-associated alterations in innate immunity with derangement of natural killer (NK) cell phenotype and function in IDR patients [15][16][17] are involved in altered monocyte and dendritic cell editing [18][19][20] with impaired recovery of CD4 + cell numbers and function. In this case, potential interventions specifically addressing innate immunity [21] could contribute to improve the response to HAART.…”

mentioning

confidence: 99%