Antiretroviral therapy partly reverses the systemic and mucosal distribution of NK cell subsets that is altered by SIVmac251 infection of macaques

Liyanage, Namal P. M.; Gordon, Shari N.; Doster, Melvin N.; Pegu, Poonam; Vaccari, Monica; Shukur, Nebiyu; Schifanella, Luca; Pise-Masison, Cynthia A.; Lipińska, Danuta; Grubczak, Kamil; Moniuszko, Marcin; Franchini, Genoveffa

doi:10.1016/j.virol.2013.12.003

Cited by 19 publications

(32 citation statements)

References 44 publications

(74 reference statements)

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“…Next, we studied mucosal ILCs comprising natural killer (NK) cells that express NKG2A and NKp44 receptors 15, 16 . Within the mucosal ILC population, NKG2A + cells mediate cytotoxicity, whereas NKp44 + cells produce IL-17, IL-22 and B cell–activating factor (BAFF), thereby promoting epithelial integrity and mucosal homeostasis 16, 17 .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Vaccari

Gordon

Fourati

et al. 2016

Nat Med

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185

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A recombinant vaccine containing Aventis Pasteur’s canarypox vector (ALVAC)–HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC–simian immunodeficiency virus (SIV) and gp120 alum (ALVAC–SIV + gp120) equivalent vaccine, but not an ALVAC–SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.

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Section: Resultsmentioning

confidence: 99%

“…At least 50,000 CD3 − singlet events (were acquired on a LSR II (BD) and analyzed using FlowJo Software (TreeStar). Mucosal NK cell were gated on live lymphocytes, which were negative for CD20 and CD3 and further classified on the basis of the expression of NKG2A and NKp44 surface markers 15, 16 .…”

Section: Methodsmentioning

confidence: 99%

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Vaccari

Gordon

Fourati

et al. 2016

Nat Med

Self Cite

185

269

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“…ART substantially expands intestinal NK cell populations despite the incomplete recovery of circulating CD4+ T cells [128, 129]. A similar impact of ART has been confirmed as well in SIV-infected Rhesus monkeys in which the initial drop of NK cells in the gut is reversed by the administration of antiviral treatment [130, 131]. …”

Section: Nk Cells and Antiretroviral Therapymentioning

confidence: 75%

Natural killer cells in HIV-1 infection and therapy

Mikulak

Oriolo

Zaghi

et al. 2017

Aids

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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 CD56neg NK cells with an aberrant repertoire of activating and inhibitory receptors. Nevertheless, the presence of specific haplotypes for NK cell receptors as well as the engagement of NK cell antibody dependent cell cytotocity (ADCC) 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 anti-viral pharmacological approaches. Indeed, the administration of antiretroviral therapy (ART) in HIV-1 infected patients restores NK cell phenotype and functions to normal levels. Thus, ART 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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“…ART has been shown to impact NK cells during SIV infection. A short course of ART (11 weeks) was recently shown to partially restore the normal distribution of systemic and mucosal NK cell subsets altered by SIV infection . We have previously reported a novel T‐cell‐dependent effector function of NK cells associated with strong and durable control of viraemia in SIV+ controlling macaques, that could be partially restored in SIV+ non‐controlling macaques by 8 weeks of ART.…”

Section: Discussionmentioning

confidence: 94%

“…A short course of ART (11 weeks) was recently shown to partially restore the normal distribution of systemic and mucosal NK cell subsets altered by SIV infection. 36 We have previously reported a novel T-cell-dependent effector function of NK cells associated with strong and durable control of viraemia in SIV+ controlling macaques, 5 that could be partially restored in SIV+ non-controlling macaques by 8 weeks of ART. In that study, only CD69 and IFN-c production by NK cells was recovered, 5 whereas here 11 weeks of ART was sufficient to rescue TNF-a production as well (Fig.…”

Section: Discussionmentioning

confidence: 96%

Therapeutic envelope vaccination in combination with antiretroviral therapy temporarily rescues SIV‐specific CD4⁺ T‐cell‐dependent natural killer cell effector responses in chronically infected rhesus macaques

et al. 2015

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SummaryNatural killer (NK) cells are essential components of the immune system, and due to their rapid response potential, can have a great impact during early anti-viral immune responses. We have previously shown that interleukin-2-dependent NK and CD4 + T-cell co-operative immune responses exist in long-term simian immunodeficiency virus (SIV) -infected controlling macaques and can be rescued in SIV-infected non-controlling macaques by a short course of antiretroviral therapy (ART). Given that co-operative responses may play an important role in disease prevention and therapeutic treatment, in the present study we sought to determine if these responses can be enhanced in chronically SIV-infected macaques by vaccination with a single-dose of envelope protein given during ART. To this end, we treated 14 chronically SIV-infected macaques with ART for 11 weeks and gave 10 of these macaques a single intramuscular dose of SIV gp120 at week 9 of treatment. ART significantly decreased plasma and mucosal viral loads, increased the numbers of circulating CD4 + T cells in all macaques, and increased T-cell-dependent envelope-and gagspecific interferon-c and tumour necrosis factor-a production by circulatory CD56 + NK cells. The therapeutic envelope immunization resulted in higher envelope-specific responses compared with those in macaques that received ART only. Functional T-cell responses restored by ART and therapeutic Env immunization were correlated with transiently reduced plasma viraemia levels following ART release. Collectively our results indicate that SIV-specific T-cell-dependent NK cell responses can be efficiently rescued by ART in chronically SIV-infected macaques and that therapeutic immunization may be beneficial in previously vaccinated individuals.

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Antiretroviral therapy partly reverses the systemic and mucosal distribution of NK cell subsets that is altered by SIVmac251 infection of macaques

Cited by 19 publications

References 44 publications

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Natural killer cells in HIV-1 infection and therapy

Therapeutic envelope vaccination in combination with antiretroviral therapy temporarily rescues SIV‐specific CD4⁺ T‐cell‐dependent natural killer cell effector responses in chronically infected rhesus macaques

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Antiretroviral therapy partly reverses the systemic and mucosal distribution of NK cell subsets that is altered by SIVmac251 infection of macaques

Cited by 19 publications

References 44 publications

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Natural killer cells in HIV-1 infection and therapy

Therapeutic envelope vaccination in combination with antiretroviral therapy temporarily rescues SIV‐specific CD4+ T‐cell‐dependent natural killer cell effector responses in chronically infected rhesus macaques

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Therapeutic envelope vaccination in combination with antiretroviral therapy temporarily rescues SIV‐specific CD4⁺ T‐cell‐dependent natural killer cell effector responses in chronically infected rhesus macaques