TLR8 combined withTLR3 or TLR4 agonists enhances DC-NK driven effector Tc1 cells

Nouri-Shirazi, Mahyar; Tamjidi, Saba; Nourishirazi, Erika; Guinet, Elisabeth

doi:10.1016/j.imlet.2017.10.015

Cited by 17 publications

(16 citation statements)

References 46 publications

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“…Furthermore, we observed a transient decrease in circulating NK cells subsets (CD56 dim ) following Poly-ICLC treatment, which may possibly reflect trafficking of this subset of NK cells to the tissues. In preclinical studies, Poly-ICLC has been shown to secondarily activate NK cells to enhance their cytotoxicity which may in turn augment the killing and elimination of latently infected cells alone (25, 55) or in combination with other TLR ligands (56).…”

Section: Discussionmentioning

confidence: 99%

Poly-ICLC, a TLR3 Agonist, Induces Transient Innate Immune Responses in Patients With Treated HIV-Infection: A Randomized Double-Blinded Placebo Controlled Trial

et al. 2019

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Objective: Toll-like receptor-3 agonist Poly-ICLC has been known to activate immune cells and induce HIV replication in pre-clinical experiments. In this study we investigated if Poly-ICLC could be used for disrupting HIV latency while simultaneously enhancing innate immune responses. Design: This was a randomized, placebo-controlled, double-blinded trial in aviremic, cART-treated HIV-infected subjects. Participants ( n = 15) were randomized 3:1 to receive two consecutive daily doses of Poly-ICLC (1.4 mg subcutaneously) vs. placebo. Subjects were observed for adverse events, immune activation, and viral replication. Methods: Besides primary outcomes of safety and tolerability, several longitudinal immune parameters were evaluated including immune cell phenotype and function via flowcytometry, ELISA, and transcriptional profiling. PCR assays for plasma HIV-1 RNA, CD4 + T cell-associated HIV-1 RNA, and proviral DNA were performed to measure HIV reservoirs and latency. Results: Poly-ICLC was overall safe and well-tolerated. Poly-ICLC-related adverse events were Grade 1/2, with the exception of one Grade 3 neutropenia which was short-lived. Mild Injection site reactions were observed in nearly all participants in the Poly-ICLC arm. Transcriptional analyses revealed upregulation of innate immune pathways in PBMCs following Poly-ICLC treatment, including strong interferon signaling accompanied by transient increases in circulating IP-10 (CXCL10) levels. These responses generally peaked by 24–48 h after the first injection and returned to baseline by day 8. CD4 + T cell number and phenotype were unchanged, plasma viral control was maintained and no significant effect on HIV reservoirs was observed. Conclusions: These finding suggest that Poly-ICLC could be safely used for inducing transient innate immune responses in treated HIV + subjects indicating promise as an adjuvant for HIV therapeutic vaccines. Trial Registration: www.ClinicalTrials.gov , identifier: NCT02071095.

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Section: Discussionmentioning

confidence: 99%

Poly-ICLC, a TLR3 Agonist, Induces Transient Innate Immune Responses in Patients With Treated HIV-Infection: A Randomized Double-Blinded Placebo Controlled Trial

et al. 2019

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“…In addition, DC adjuvants are also key to induce DC maturation and activation and, thus, intensify the immune response. Various combinations of cytokines, TLR agonists, and CD40 ligands have been utilized with different DC vaccines [4, 9].…”

Section: Introductionmentioning

confidence: 99%

Dendritic cells pulsed with placental gp96 promote tumor-reactive immune responses

et al. 2019

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Defining and loading of immunogenic and safe cancer antigens remain a major challenge for designing dendritic cell (DC)-based cancer vaccines. In this study, we defined a prototype strategy of using DC-based vaccines pulsed with placenta-derived heat shock protein gp96 to induces anti-tumor T cell responses. Placental gp96 was efficiently taken up by CD11c+ bone marrow-derived DCs (BMDCs) and resulted in moderate BMDC maturation. Splenocytes and cytotoxic T cells (CTLs) generated with mouse BMDCs pulsed with placental gp96 specifically lysed B16 melanoma and LLC lung carcinoma cells. In both transplantable melanoma and lung carcinoma mice models, immunization with placental gp96-stimulated BMDCs led to a significant decrease in tumor growth and mouse mortality with respect to mice treated with liver gp96-pulsed BMDCs or placental gp96 alone. This vaccine induced strong cross-reactive tumor-specific T cell responses. Our results revealed that DCs pulsed with placenta-derived gp96 represent an effective immunotherapy to induce tumor-reactive immune responses, possibly via loading DCs with its associated carcinoembryonic antigens.

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“…This indicates that a co-stimulation of at least two TLRs is needed to build a robust IL12p70 induction. Similarly, significantly enhanced DC maturation and IFNγ production of NK cells has been found after co-stimulation with TLR8 and either TLR3 or -4 [67]. Using Poly(I:C)-encapsulating nanoparticles as a TLR3 agonist after BCG infection or specific TLR2 activation led to synergistic production of nitric oxide (NO) in mural BMDM [68].…”

Section: Synergy Of Different Prrsmentioning

confidence: 95%

RNA Sensing of Mycobacterium tuberculosis and Its Impact on TB Vaccination Strategies

Burkert

Schumann

2020

Vaccines

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Tuberculosis (TB) is still an important global threat and although the causing organism has been discovered long ago, effective prevention strategies are lacking. Mycobacterium tuberculosis (MTB) is a unique pathogen with a complex host interaction. Understanding the immune responses upon infection with MTB is crucial for the development of new vaccination strategies and therapeutic targets for TB. Recently, it has been proposed that sensing bacterial nucleic acid in antigen-presenting cells via intracellular pattern recognition receptors (PRRs) is a central mechanism for initiating an effective host immune response. Here, we summarize key findings of the impact of mycobacterial RNA sensing for innate and adaptive host immunity after MTB infection, with emphasis on endosomal toll-like receptors (TLRs) and cytosolic sensors such as NLRP3 and RLRs, modulating T-cell differentiation through IL-12, IL-21, and type I interferons. Ultimately, these immunological pathways may impact immune memory and TB vaccine efficacy. The novel findings described here may change our current understanding of the host response to MTB and potentially impact clinical research, as well as future vaccination design. In this review, the current state of the art is summarized, and an outlook is given on how progress can be made.

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TLR8 combined withTLR3 or TLR4 agonists enhances DC-NK driven effector Tc1 cells

Abstract: Our data indicate that if in need of an enhanced DC-NK mediated cellular immunity one may select TLR agonists with defined synergistic effects.

Cited by 17 publications

References 46 publications

Poly-ICLC, a TLR3 Agonist, Induces Transient Innate Immune Responses in Patients With Treated HIV-Infection: A Randomized Double-Blinded Placebo Controlled Trial

Poly-ICLC, a TLR3 Agonist, Induces Transient Innate Immune Responses in Patients With Treated HIV-Infection: A Randomized Double-Blinded Placebo Controlled Trial

Dendritic cells pulsed with placental gp96 promote tumor-reactive immune responses

RNA Sensing of Mycobacterium tuberculosis and Its Impact on TB Vaccination Strategies

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