Activation of cytokine-producing and antitumor activities of natural killer cells and macrophages by engagement of Toll-like and NOD-like receptors

Fu, Qin; Maniar, A. C.; Diaz, Marco Quevedo; Chapoval, Andrei I.; Medvedev, Andrei E.

doi:10.1177/1753425910372000

Cited by 38 publications

(15 citation statements)

References 61 publications

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“…First, we tested the above TLR agonists in their ability to reactivate latent HIV-1 in three other models of latency. Second, we tested their ability to induce IL-8 production in the promonocytic cell line THP-1 [ 27 ]. As shown in Additional file 1 : Figure S1A, Flagellin was able to reactivate latent HIV-1 in the J-Lat clone 10.6 as previously described [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Reactivation of latent HIV-1 in central memory CD4+T cells through TLR-1/2 stimulation

et al. 2013

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BackgroundToll-like receptors (TLRs) are crucial for recognition of pathogen-associated molecular patterns by cells of the innate immune system. TLRs are present and functional in CD4+ T cells. Memory CD4+ T cells, predominantly central memory cells (TCM), constitute the main reservoir of latent HIV-1. However, how TLR ligands affect the quiescence of latent HIV within central memory CD4+ T cells has not been studied.ResultsWe evaluated the ability of a broad panel of TLR agonists to reactivate latent HIV-1. The TLR-1/2 agonist Pam3CSK4 leads to viral reactivation of quiescent HIV in a model of latency based on cultured TCM and in resting CD4+ T cells isolated from aviremic patients. In addition, we investigated the signaling pathway associated with Pam3CSK4 involved in HIV-1 reactivation. We show that the transcription factors NFκB, NFAT and AP-1 cooperate to induce viral reactivation downstream of TLR-1/2 stimulation. Furthermore, increasing levels of cyclin T1 is not required for TLR-mediated viral reactivation, but induction of viral expression requires activated pTEFb. Finally, Pam3CSK4 reactivates latent HIV-1 in the absence of T cell activation or proliferation, in contrast to antigen stimulation.ConclusionsOur findings suggest that the signaling through TLR-1/2 pathway via Pam3CSK4 or other reagents should be explored as an anti-latency strategy either alone or in combination with other anti-latency drugs.

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Section: Resultsmentioning

confidence: 99%

Reactivation of latent HIV-1 in central memory CD4+T cells through TLR-1/2 stimulation

et al. 2013

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“…The NOD2-like receptors (NLRs) belong to evolution-conserved pattern recognition receptors (PRRs) family locating in cytoplasm, closely related to responses, innate immunity and adaptive immunity [ 1 ]. NLRs are expressed in various cell types, including macrophage, neutrophils, epithelial and endothelial cells, dendritic cells, as well as in malignant tumors [ 19 ]. Genetic variations in NOD1 and NOD2 are associated with increased susceptibility to Crohn's disease [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

NOD2 maybe a biomarker for the survival of kidney cancer patients

Zhang

et al. 2017

Oncotarget

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BackgroundNucleotide-binding oligomerization domain-containing protein 2 (NOD2) may play an important role in the outcome of kidney cancer patients. To explore the relationship between NOD2 and the prognosis of kidney cancer patients, a databank-based reanalysis was conducted.Materials and MethodsData related to kidney cancer patients at least with survival information, was obtained mainly from The Cancer Genome Atlas (TCGA). Some clinical data, not available online, was collected by personal email to the author. Then, we reanalyzed all the data in order to make a conclusion about the relationship between NOD2 gene and the prognosis of kidney cancer patients.ResultsA total of 1953 samples with NOD2 information from four databanks of The Cancer Genome Atlas (TCGA) were enrolled in this study. The results of KIPAN showed the Kaplan-Meier curve for risk groups, concordance index, and p-value of the log-rank testing equality of survival curves ( Concordance Index = 56.57, Log−Rank Equal Curves p=0.0009006, R^2 = 0.036/0.953, Risk Groups Hazard Ratio = 1.61 (conf. int. 1.21 ~ 2.13), p = 0.001005) , while a box plot across risk groups, including the p-value testing for difference using t-test (or f-test for more than two groups) was shown. There was a statistical significance for the p value of the result (p < 0.01 ). The similar results could be seen in KIRC and the fourth data (including 468 samples).ConclusionsThe status of NOD2 gene maybe a biomarker for the survival of kidney cancer patients.

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“…In contrast, a different study found that engagement of TLR3 on human CD8+ T cells had no effect on their cytolytic activity [19]. Human peripheral blood NK cells reportedly express high levels of TLR3, TLR7, and TLR9 and stimulation with ligands led to an increase in IFN-γ production [22]. In a mouse model of COPD, NK cells from smoke-exposed mice produced more IFN-γ following stimulation with the ligands for TLR3, TLR7, and TLR9 than NK cells from mice exposed to filtered air [23].…”

Section: Introductionmentioning

confidence: 99%

Lung CD8+ T cells in COPD have increased expression of bacterial TLRs

et al. 2013

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BackgroundToll-like receptors (TLRs) on T cells can modulate their responses, however, the extent and significance of TLR expression by lung T cells, NK cells, or NKT cells in chronic obstructive pulmonary disease (COPD) is unknown.MethodsLung tissue collected from clinically-indicated resections (n = 34) was used either: (a) to compare the expression of TLR1, TLR2, TLR2/1, TLR3, TLR4, TLR5, TLR6 and TLR9 on lung CD8+ T cells, CD4+ T cells, NK cells and NKT cells from smokers with or without COPD; or (b) to isolate CD8+ T cells for culture with anti-CD3ε without or with various TLR ligands. We measured protein expression of IFN-γ, TNF-α, IL-13, perforin, granzyme A, granzyme B, soluble FasL, CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL9 in supernatants.ResultsAll the lung subsets analyzed demonstrated low levels of specific TLR expression, but the percentage of CD8+ T cells expressing TLR1, TLR2, TLR4, TLR6 and TLR2/1 was significantly increased in COPD subjects relative to those without COPD. In contrast, from the same subjects, only TLR2/1 and TLR2 on lung CD4+ T cells and CD8+ NKT cells, respectively, showed a significant increase in COPD and there was no difference in TLR expression on lung CD56+ NK cells. Production of the Tc1 cytokines IFN-γ and TNF-α by lung CD8+ T cells were significantly increased via co-stimulation by Pam3CSK4, a specific TLR2/1 ligand, but not by other agonists. Furthermore, this increase in cytokine production was specific to lung CD8+ T cells from patients with COPD as compared to lung CD8+ T cells from smokers without COPD.ConclusionsThese data suggest that as lung function worsens in COPD, the auto-aggressive behavior of lung CD8+ T cells could increase in response to microbial TLR ligands, specifically ligands against TLR2/1.

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Activation of cytokine-producing and antitumor activities of natural killer cells and macrophages by engagement of Toll-like and NOD-like receptors

Cited by 38 publications

References 61 publications

Reactivation of latent HIV-1 in central memory CD4+T cells through TLR-1/2 stimulation

Reactivation of latent HIV-1 in central memory CD4+T cells through TLR-1/2 stimulation

NOD2 maybe a biomarker for the survival of kidney cancer patients

Lung CD8+ T cells in COPD have increased expression of bacterial TLRs

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