Expression of Interleukin-15 and Interleukin-15Rα in Monocytes of HIV Type 1-Infected Patients with Different Courses of Disease Progression

Tarkowski, Maciej; Ferraris, Laurenzia; Martone, S.; Castillia, Francesco Strambio de; Misciagna, D.; Mazzucchelli, Renata; Lattuada, Emanuela; Paraninfo, Giuseppe; Galli, Massimo

doi:10.1089/aid.2010.0317

Cited by 15 publications

(10 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with prior studies, plasma sCD14 correlated not only with IL-6 [18] , [55] , but also with IL-15 [22] , [56] . Elevated IL-15 is associated with higher plasma VL during acute HIV infection [38] , while IL-15 is expressed at higher levels in monocytes from HIV-infected long-term nonprogressors compared to progressors or uninfected controls [57] . IL-15 is a Th1 cytokine expressed on monocytes upon activation that shares activities with IL-2, such as stimulation of T cell proliferation and activation, but also stimulates cell adhesion and production of proinflammatory cytokines [58] and NK cell functions, including secretion of IFNγ and CCR5 ligands [59] , [60] .…”

Section: Discussionmentioning

confidence: 99%

A Plasma Biomarker Signature of Immune Activation in HIV Patients on Antiretroviral Therapy

et al. 2012

View full text Add to dashboard Cite

BackgroundImmune activation is a strong predictor of disease progression in HIV infection. Combinatorial plasma biomarker signatures that represent surrogate markers of immune activation in both viremic and aviremic HIV patients on combination antiretroviral therapy (cART) have not been defined. Here, we identify a plasma inflammatory biomarker signature that distinguishes between both viremic and aviremic HIV patients on cART and healthy controls and examine relationships of this signature to markers of disease progression.MethodsMultiplex profiling and ELISA were used to detect 15 cytokines/chemokines, soluble IL-2R (sIL-2R), and soluble CD14 (sCD14) in plasma from 57 HIV patients with CD4 nadir <300 cells/µl and 29 healthy controls. Supervised and unsupervised analyses were used to identify biomarkers explaining variance between groups defined by HIV status or drug abuse. Relationships between biomarkers and disease markers were examined by Spearman correlation.ResultsThe majority (91%) of HIV subjects were on cART, with 38% having undetectable viral loads (VL). Hierarchical clustering identified a biomarker cluster in plasma consisting of two interferon-stimulated gene products (CXCL9 and CXCL10), T cell activation marker (sIL-2R), and monocyte activation marker (sCD14) that distinguished both viremic and aviremic HIV patients on cART from controls (p<0.0001) and were top-ranked in variables important in projection plots. IL-12 and CCL4 were also elevated in viremic and aviremic patients compared to controls (p<0.05). IL-12 correlated with IFNα, IFNγ, CXCL9, and sIL-2R (p<0.05). CXCL10 correlated positively with plasma VL and percentage of CD16+ monocytes, and inversely with CD4 count (p = 0.001, <0.0001, and 0.04, respectively).ConclusionA plasma inflammatory biomarker signature consisting of CXCL9, CXCL10, sIL-2R, and sCD14 may be useful as a surrogate marker to monitor immune activation in both viremic and aviremic HIV patients on cART during disease progression and therapeutic responses.

show abstract

Section: Discussionmentioning

confidence: 99%

A Plasma Biomarker Signature of Immune Activation in HIV Patients on Antiretroviral Therapy

et al. 2012

View full text Add to dashboard Cite

show abstract

“…One of the most significant changes in this pathway was the effective and systematic down-regulation of genes encoding pro-inflammatory cytokines, including IL-1B, IL-6, IL-8, TNF-α, in the viremia group. Interestingly, the core-enriched gene IL-15 shares many activities with IL-2 and is down-regulated in patients with viremia, and was also found to be expressed at significantly higher levels in LTNPs monocytes than in people with HIV progression ( 75 ). Finally, a study has shown that at least one host genetic factor (HLA, chemokine receptors is associated with slow HIV progression ( 76 ).…”

Section: Participation In the Innate Immune Pathway Of Hiv Infection ...mentioning

confidence: 99%

The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection

Shi

Chen

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

The natural process of human immunodeficiency virus type 1(HIV-1) infection is characterized by high viral load, immune cell exhaustion, and immunodeficiency, which eventually leads to the stage of acquired immunodeficiency syndrome (AIDS) and opportunistic infections. Rapidly progressing HIV-1 individuals often die of AIDS several years after infection without treatment. The promotion of ART greatly prolongs the survival time of HIV-infected persons. However, some patients have incomplete immune function reconstruction after ART due to latent storage of HIV-infected cells. Therefore, how to achieve a functional cure has always been the focus and hot spot of global AIDS research. Fortunately, the emergence of ECs/LTNPs who can control virus replication naturally has ignited new hope for realizing a functional cure for AIDS. Recently, a special category of infected individuals has attracted attention that can delay the progression of the disease more rigorously than the natural progression of HIV-1 infection described above. These patients are characterized by years of HIV-1 infection, long-term asymptomatic status, and normal CD4+T cell count without ART, classified as HIV-infected long-term nonprogressors (LTNPs) and elite controllers (ECs). Numerous studies have shown that the host and virus jointly determine the progression of HIV-1 infection, in which the level of innate immunity activation plays an important role. As the first line of defense against pathogen invasion, innate immunity is also a bridge to induce adaptive immunity. Compared with natural progressors, innate immunity plays an antiviral role in HIV-1 infection by inducing or activating many innate immune-related factors in the natural ECs. Learning the regulation of ECs immunity, especially the innate immunity in different characteristics, and thus studying the mechanism of the control of disease progression naturally, will contribute to the realization of the functional cure of AIDS. Therefore, this review will explore the relationship between innate immunity and disease progression in ECs of HIV-1 infection from the aspects of innate immune cells, signaling pathways, cytokines, which is helpful to provide new targets and theoretical references for the functional cure, prevention and control of AIDS, and development of a vaccine.

show abstract

“…In a previous study of the same group, IL-15 priming was shown to induce a significant increase of IFN-gamma production in both viremic and aviremic HIV-positive patients [ 132 ]. Tarkowski et al [ 133 ] found that the expression of IL-15, but not of its receptor IL-15R α , was significantly higher in the CD14+ monocytes of long-term nonprogressors than in those of HIV-1 progressors or healthy controls; differences in IL-15 expression between patients with different courses of HIV infection may be indicative of a potential use of this cytokine as a therapeutic agent.…”

Section: Potential Strategies To Reduce Residual Viremia and Enhanmentioning

confidence: 99%

HIV RNA Suppression and Immune Restoration: Can We Do Better?

Pinzone

Rosa

Cacopardo

et al. 2012

Clinical and Developmental Immunology

View full text Add to dashboard Cite

HAART has significantly changed the natural history of HIV infection: patients receiving antiretrovirals are usually able to control viremia, even though not all virological responders adequately recover their CD4+ count. The reasons for poor immune restoration are only partially known and they include genetic, demographic and immunologic factors. A crucial element affecting immune recovery is immune activation, related to residual viremia; indeed, a suboptimal virological control (i.e., low levels of plasma HIV RNA) has been related with higher levels of chronic inflammation and all-cause mortality. The sources of residual viremia are not yet completely known, even though the most important one is represented by latently infected cells. Several methods, including 2-LTR HIV DNA and unspliced HIV RNA measurement, have been developed to estimate residual viremia and predict the outcome of antiretroviral therapy. Considering that poor immunologic responders are exposed to a higher risk of both AIDS-related and non-AIDS-related diseases, there is a need of new therapeutic strategies, including immunomodulators and drugs targeting the latent viral reservoirs, in order to face residual viremia but also to “drive” the host immunologic responses.

show abstract

Expression of Interleukin-15 and Interleukin-15Rα in Monocytes of HIV Type 1-Infected Patients with Different Courses of Disease Progression

Cited by 15 publications

References 53 publications

A Plasma Biomarker Signature of Immune Activation in HIV Patients on Antiretroviral Therapy

A Plasma Biomarker Signature of Immune Activation in HIV Patients on Antiretroviral Therapy

The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection

HIV RNA Suppression and Immune Restoration: Can We Do Better?

Contact Info

Product

Resources

About