scholarly journals Abnormal intracellular IL-2 and interferon-gamma (IFN-γ) production as HIV-1-associated markers of immune dysfunction

1998 ◽  
Vol 111 (2) ◽  
pp. 257-263 ◽  
Author(s):  
Westby ◽  
Marriott ◽  
Guckian ◽  
Cookson ◽  
Hay ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Immune Dysfunction ◽  
Ifn Γ ◽  
Hiv 1

scholarly journals Control of the HIV-1 DNA Reservoir Is Associated In Vivo and In Vitro with NKp46/NKp30 (CD335 CD337) Inducibility and Interferon Gamma Production by Transcriptionally Unique NK Cells

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Francesco Marras ◽  
Anna Casabianca ◽  
Federica Bozzano ◽  
Maria Libera Ascierto ◽  
Chiara Orlandi ◽  
...  
Keyword(s):  
Nk Cells ◽  
Interferon Gamma ◽  
Antiretroviral Treatment ◽  
Nk Cell ◽  
Transcriptional Signature ◽  
Hiv Dna ◽  
Ifn Γ ◽  
Hiv 1 ◽  
Dna Reservoir

ABSTRACT The size of lentiviral DNA reservoirs reflects the effectiveness of immune responses against lentiviruses. So far, abundant information has been gathered on the control of HIV-1 replication. Understanding the innate mechanisms contributing to containment of the HIV DNA reservoir, however, are only partly clarified and are relevant to guiding interventions for reservoir containment or eradication. We studied the contribution of natural killer (NK) cell functional features in HIV patients controlling replication either spontaneously (HIV controllers [HIC]) or after progression and antiretroviral treatment (progressor patients [PP]). An inverse correlation between HIV DNA copy numbers (either total or integrated) in circulating CD4+ cells and NK cell function was observed. Induced interferon gamma (IFN-γ) production and NKp46/NKp30 activating receptor-induced expression correlated inversely with reservoir size. The correlation was present not only for a homogeneous cohort of HIC patients but also when PP were included in the analysis. Adaptive (NKG2C+ CD57+) NK cell features were not associated with reservoir size. However, a distinct set of 370 differentially expressed transcripts was found to underlie functional differences in NK cells controlling HIV DNA reservoir size. In proof-of-principle in vitro experiments of CD4+ cell infection with HIV-1, purified NK cells with the above-mentioned functional/transcriptional features displayed 10- and 30-fold higher abilities to control HIV replication and DNA burdens in vitro, respectively, than those of other NK cells. Thus, NK cells with a specific functional and transcriptional signature contribute to control of the HIV reservoir in CD4+ cells. Their selection, expansion, and/or adoptive transfer may support strategies to eradicate HIV-1 infection or to safely deescalate antiretroviral treatment. IMPORTANCE The most relevant feature of HIV-1 infection is represented by its DNA reservoir size in the body, which guarantees lifelong infection and resumption of virus replication after antiretroviral treatment interruption. So far, there has been little success in the identification of factors contributing to HIV-1 reservoir containment. In this study, by studying quantitative total and integrated HIV-1 DNA levels and NK cells in HIV-1 patients with either progressive or nonprogressive disease, we observed that inducible IFN-γ and natural cytotoxicity receptor (NCR) expression in a specific subset of NK cells with a characteristic transcriptional signature represents a correlate for HIV-1 reservoir control. This represents an advance in our understanding of the mechanism(s) that controls the lentivirus reservoir. Monitoring, selection, expansion, and adoptive transfer of these NK cells may allow monitoring of treatment efficacy and the likelihood of reservoir control and may support protocols for HIV-1 eradication.

Interleukin-4 and Interferon-Gamma Production during HIV-1 Infection and Changes Induced by Antiretroviral Therapy

2003 ◽  
Vol 16 (2) ◽  
pp. 157-166 ◽  
Author(s):  
J. Vecchiet ◽  
M. Dalessandro ◽  
F. Travasi ◽  
K. Falasca ◽  
A. Di Iorio ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Interferon Gamma ◽  
Highly Active Antiretroviral Therapy ◽  
Interleukin 4 ◽  
In Vitro Production ◽  
Mean Values ◽  
Ifn Γ ◽  
Hiv 1

Several lines of evidence indicate that a switch of the cytokine pattern from a predominant type 1 (antiviral and cell mediated response) to type 2 (polyclonal humoral immune response) occurs during the course of Human Immunodeficiency Virus-1 (HIV-1) infection, and represents a key event in the progression of immunodeficiency and dysregulated immune activation. We proposed to further investigate this immunological aspect of HIV-1 disease, in naive and in patients treated with Highly Active Antiretroviral Therapy (HAART). The prototypic cytokines chosen were Interleukin (IL)-4 and Interferon-gamma (IFN-γ), whose in vitro production was determined in mononuclear cell cultures stimulated with different T lymphocyte mitogenic agents (anti-CD3, Phytohaemoagglutin-P -PHA-, E. coli B04/035 Lipopolysaccharide -LPS-). We classified all the patients on the basis of the number of CD4+ lymphocytes and we found a progressive, even if not significant decrease in the baseline production of IFN-γ with the progression of the immunodeficiency. The mean value of baseline IFN-γ in the group of patients with CD4+>500 cells/μL was 7.79+3.1 pg/mL while in the group with CD4+<200 cells/μL it was 4.66±2.22. We didn't find significant differences in the baseline production of IL-4 in these groups and in IFN-γ and IL-4 production in LPS-stimulated cultures. We also re-assessed 12 patients after one year's follow-up. They presented a significant increase in IFN-γ production compared to the first assessment in the LPS-stimulated cultures (baseline IFN-γ 2.87+1.17 pg/mL, after 12 months 19.15±5.19 pg/mL; p= 0.03). In the 12 patients in follow-up IL-4 production showed a decreased in PHA-stimulated cultures with mean values of 16.65±14.32 pg/mL at baseline and 6.54±6.54 pg/mL after follow-up. These results highlight the immunorestoring effects of HAART. IL-4 production was lower in the treated subjects compared to the naive ones in PHA-stimulated cultures (mean values: IL-4=13.42 ±11.08 pg/mL in the naive patients and 9.75 ±65 pg/mL in the treated patients). The IFN-γ values in anti-CD3 stimulated cultures were also higher in the treated patients, but this increase was not significant.

scholarly journals The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Tonya Kueck ◽  
Elena Cassella ◽  
Jessica Holler ◽  
Baek Kim ◽  
Paul D Bieniasz
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Interferon Gamma ◽  
Transcriptional Repression ◽  
Cyclin Dependent Kinase ◽  
Antiviral Signaling ◽  
Aryl Hydrocarbon ◽  
Antiviral Effects ◽  
Ifn Γ ◽  
Hiv 1 ◽  
Hsv 1

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activation induces the expression of numerous genes, with many effects on cells. However, AhR activation is not known to affect the replication of viruses. We show that AhR activation in macrophages causes a block to HIV-1 and HSV-1 replication. We find that AhR activation transcriptionally represses cyclin-dependent kinase (CDK)1/2 and their associated cyclins, thereby reducing SAMHD1 phosphorylation, cellular dNTP levels and both HIV-1 and HSV-1 replication. Remarkably, a different antiviral stimulus, interferon gamma (IFN-γ), that induces a largely non-overlapping set of genes, also transcriptionally represses CDK1, CDK2 and their associated cyclins, resulting in similar dNTP depletion and antiviral effects. Concordantly, the SIV Vpx protein provides complete and partial resistance to the antiviral effects of AhR and IFN-γ, respectively. Thus, distinct antiviral signaling pathways converge on CDK/cyclin repression, causing inhibition of viral DNA synthesis and replication.

scholarly journals Consistency ofMycobacterium tuberculosis-Specific Interferon-Gamma Responses in HIV-1-Infected Women during Pregnancy and Postpartum

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Sasi R. Jonnalagadda ◽  
Elizabeth Brown ◽  
Barbara Lohman-Payne ◽  
Dalton Wamalwa ◽  
Carey Farquhar ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Interferon Gamma ◽  
Mixed Models ◽  
Odds Ratio ◽  
Pregnancy And Postpartum ◽  
Latent Tb ◽  
Ifn Γ ◽  
One Year ◽  
Latent Tb Infection ◽  
Hiv 1

Background. We determined the consistency of positive interferon-gamma (IFN-γ) release assays (IGRAs) to detect latent TB infection (LTBI) over one-year postpartum in HIV-1-infected women.Methods. Women with positive IGRAs during pregnancy had four 3-monthly postpartum IGRAs. Postpartum change in magnitude of IFN-γ response was determined using linear mixed models.Results. Among 18 women with positive pregnancy IGRA, 15 (83%) had a subsequent positive IGRA; 9 (50%) were always positive, 3 (17%) were always negative, and 6 (33%) fluctuated between positive and negative IGRAs. Women with pregnancy IGRA IFN-γ>8spot forming cells (SFCs)/well were more likely to have consistent postpartum IGRA response (odds ratio: 10.0; 95% confidence interval (CI): 0.9–117.0). Change in IFN-γ response over postpartum was 10.2 SFCs/well (95% CI: −1.5–21.8 SFCs/well).Conclusion. Pregnancy positive IGRAs were often maintained postpartum with increased consistency in women with higher baseline responses. There were modest increases in magnitude of IGRA responses postpartum.

scholarly journals The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression

2018 ◽  
Author(s):  
Tonya Kueck ◽  
Elena Cassella ◽  
Jessica Holler ◽  
Baek Kim ◽  
Paul D. Bieniasz
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Interferon Gamma ◽  
Transcriptional Repression ◽  
Cyclin Dependent Kinase ◽  
Antiviral Signaling ◽  
Aryl Hydrocarbon ◽  
Antiviral Effects ◽  
Ifn Γ ◽  
Hiv 1 ◽  
Hsv 1

SummaryThe aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activation induces the expression of numerous genes, with many effects on cells. However, AhR activation is not known to affect the replication of viruses. We show that AhR activation in macrophages causes a block to HIV-1 and HSV-1 replication. We find that AhR activation transcriptionally represses cyclin-dependent kinase (CDK)1/2 and their associated cyclins, thereby reducing SAMHD1 phosphorylation, cellular dNTP levels and both HIV-1 and HSV-1 replication. Remarkably, a different antiviral stimulus, interferon gamma (IFN-γ), that induces a largely non-overlapping set of genes, also transcriptionally represses CDK1, CDK2 and their associated cyclins, resulting in similar dNTP depletion and antiviral effects. Concordantly, the SIV Vpx protein provides complete and partial resistance to the antiviral effects of AhR and IFN-γ, respectively. Thus, distinct antiviral signaling pathways converge on CDK/cyclin repression, causing inhibition of viral DNA synthesis and replication.

scholarly journals Protective Effect of Membrane-Free Stem Cells against Lipopolysaccharide and Interferon-Gamma-Stimulated Inflammatory Responses in RAW 264.7 Macrophages

2021 ◽  
Vol 22 (13) ◽  
pp. 6894
Author(s):  
Mei Tong He ◽  
Hye Sook Park ◽  
Young Sil Kim ◽  
Ah Young Lee ◽  
Eun Ju Cho
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Interferon Gamma ◽  
Mapk Signaling ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Protein Expressions ◽  
Ifn Γ ◽  
Cox 2 ◽  
Anti Inflammatory

Recently, adipose-derived stem cells (ADSCs) are considered to be ideal for application in cell therapy or tissue regeneration, mainly due to their wide availability and easy access. In this study, we examined the anti-inflammatory effects of membrane-free stem cell extract (MFSC-Ex) derived from ADSCs against lipopolysaccharide (LPS)/interferon-gamma (IFN-γ) on RAW 264.7 macrophage cells. Exposure of RAW macrophages to LPS and IFN-γ stimuli induced high levels of nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) production. However, pretreatment with MFSC-Ex inhibited LPS/IFN-γ-induced these pro-inflammatory mediators. To clarify the molecular mechanisms underlying the anti-inflammatory property of MFSC-Ex, we analyzed nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) protein expressions by Western blotting. Our study showed that treatment of MFSC-Ex significantly down-regulated inducible nitric oxide synthase (iNOS) and COX-2 protein expressions. Furthermore, phosphorylation of extracellular signal-regulated kinase (ERK) and p38 was also blocked by treatment with MFSC-Ex, indicating that inhibitory effect of MFSC-Ex on MAPK signaling cascade may attribute to inactivation of NF-κB. From these findings, we suggest that MFSC-Ex exert anti-inflammatory activities, which suppressed LPS/IFN-γ-induced production of NO, COX-2 and PGE2 by regulation of NF-κB and MAPK signaling pathway in RAW 264.7 macrophages. In conclusion, MFSC-Ex might provide a new therapeutic opportunity to treatment of inflammatory-related diseases.

scholarly journals CD8+ T lymphocyte is a main source of interferon-gamma production in Takayasu’s arteritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan-Long Ren ◽  
Tao-Tao Li ◽  
Wei Cui ◽  
Li-Min Zhao ◽  
Na Gao ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Lymphocyte Subsets ◽  
Takayasu’S Arteritis ◽  
Control Group ◽  
Takayasu's Arteritis ◽  
Cd8 T Lymphocyte ◽  
Healthy Control ◽  
Ifn Γ

AbstractInterferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu’s arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P < 0.05). The percentage of CD3+IFN-γ+ cells in peripheral blood CD3+ cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3+CD8+IFN-γ+ cells/CD3+IFN-γ+ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3+CD4+IFN-γ+/ CD3+CD8+IFN-γ+ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3+CD8+IFN-γ+/CD3+IFN-γ+ ratio was positively correlated with CD3+IFN-γ+cells/ CD3+cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3+CD4+IFN-γ+/CD3+IFN-γ+ ratio (r = − 0.845, P < 0.001). IFN-γ secreted by CD3+CD8 + T cells is an important source of serum IFN-γ in TAK patients.

In vitro effect of ochratoxin A and deoxynivalenol on the expression of interleukin 5 and interferon-gamma in broiler chicken lymphocytes

2016 ◽  
Vol 9 (2) ◽  
pp. 299-304 ◽  
Author(s):  
C. Lautert ◽  
L. Ferreiro ◽  
M.I. Azevedo ◽  
S.A. Botton ◽  
J.T. Santos ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Interferon Gamma ◽  
Broiler Chickens ◽  
Broiler Chicken ◽  
Fungal Metabolites ◽  
Interleukin 5 ◽  
T Helper 2 ◽  
Ifn Γ ◽  
Vitro Effect

Cytokines are proteins secreted by cells of innate and acquired immunity, produced in response to various antigens and responsible for mediating several function of these cells. Our study evaluated the profile of cytokines interleukin 5 (IL-5) and interferon gamma (IFN-γ), induced in lymphocytes of broiler chickens in response to secondary fungal metabolites ochratoxin A (OTA) and deoxynivalenol (DON) at concentrations of 0.001, 0.01, 0.1 and 1 μg/ml. The quantification of the cytokines was analysed at 24, 48 and 72 h after incubation with mycotoxins, using real-time PCR (qRT-PCR). The results obtained showed that OTA induced mRNA synthesis of IL-5 at concentrations 0.001, 0.1 and 1 μg/ml after 24 h of lymphocyte incubation, while at 48 h only the expression of the IL-5 cytokine at a concentration of 1 μg/ml (P<0.05) was detected. DON in a concentration of 1 μg/ml induced the expression of IL-5 in the lymphocytes only at 48 h post-incubation period (P<0.05). Regarding IFN-γ, gene expression was not observed in the lymphocytes of broiler chickens incubated with OTA and DON. The data obtained represent a profile of response mediated by T helper 2 cells to the exposure of broiler chicken immune cells to different concentrations of OTA and DON.

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