Modulation of heme oxygenase-1 by metalloporphyrins increases anti-viral T cell responses

Bunse, Carola E.; Fortmeier, V; Tischer, Sabine; Zilian, Eva; Figueiredo, Constança; Witte, Torsten; Blasczyk, Rainer; Immenschuh, Stephan

doi:10.1111/cei.12451

Cited by 15 publications

(15 citation statements)

References 52 publications

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“…These observations were consistent with data showing an augmented priming of antigen‐specific T cells by DCs in which HO‐1 was inhibited by SnPP . Similar results have been obtained with the HO‐1 inhibitory molecule Tin mesoporphyrin, which increased the capacity of cytomegalovirus pp65 ‐peptide‐pulsed peripheral blood mononuclear cells to prime virus‐specific naive T cells . Consistently with the ability of HO‐1 to down‐modulate the capacity of DCs to prime T cells, improved graft acceptance and reduced leucocyte infiltration were observed in an allogeneic aorta rat transplantation model after virus‐mediated Hmox1 gene transfer .…”

Section: The Ho‐1–co System As a Modulator Of Antigen Presentation Bysupporting

confidence: 89%

“…75 Similar results have been obtained with the HO-1 inhibitory molecule Tin mesoporphyrin, which increased the capacity of cytomegalovirus pp65 -peptide-pulsed peripheral blood mononuclear cells to prime virus-specific naive T cells. 77 Consistently with the ability of HO-1 to down-modulate the capacity of DCs to prime T cells, improved graft acceptance and reduced leucocyte infiltration were observed in an allogeneic aorta rat transplantation model after virus-mediated Hmox1 gene transfer. 59 Notably, both reduced leucocyte recruitment and tissue acceptance were reproduced in CO-treated animals, 59,78 suggesting that this gas was the molecule responsible for the HO-1mediated inhibition of T-cell activation.…”

Section: Regulation Of Ho-1 Gene Expressionsupporting

confidence: 56%

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Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

et al. 2016

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SummaryHaem-oxygenase-1 (HO-1) is an enzyme responsible for the degradation of haem that can suppress inflammation, through the production of carbon monoxide (CO). It has been shown in several experimental models that genetic and pharmacological induction of HO-1, as well as non-toxic administration of CO, can reduce inflammatory diseases, such as endotoxic shock, type 1 diabetes and graft rejection. Recently, it was shown that the HO-1/CO system can alter the function of antigen-presenting cells (APCs) and reduce T-cell priming, which can be beneficial during immune-driven inflammatory diseases. The molecular mechanisms by which the HO-1 and CO reduce both APC-and T-cell-driven immunity are just beginning to be elucidated. In this article we discuss recent findings related to the immune regulatory capacity of HO-1 and CO at the level of recognition of pathogen-associated molecular patterns and T-cell priming by APCs. Finally, we propose a possible regulatory role for HO-1 and CO over the recently described mitochondria-dependent immunity. These concepts could contribute to the design of new therapeutic tools for inflammation-based diseases.

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Section: The Ho‐1–co System As a Modulator Of Antigen Presentation Bysupporting

confidence: 89%

Section: Regulation Of Ho-1 Gene Expressionsupporting

confidence: 56%

Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

et al. 2016

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“…This is the first evidence that HO-1 inhibition with SnMsP improves the antigen-specific proliferative response in lymph node cells of infected dogs. Previous studies in humans have shown that SnMsP increases unspecific proliferation of T CD3+ cells (Bunse et al, 2015;Burt et al, 2010) through inducing expression of costimulatory molecules on monocytes, such as CD86 (B7-2), and optimizing the antigen presentation process (Burt et al, 2010). In CVL, it is already known that the proliferative response of T lymphocytes is reduced due to suppression of B7 molecules in the macrophages of infected dogs (Pinelli et al, 1999a,b).…”

Section: Discussionmentioning

confidence: 99%

The effects of increased heme oxygenase-1 on the lymphoproliferative response in dogs with visceral leishmaniasis

et al. 2017

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Canine visceral leishmaniasis (CVL) is known to affect the cellular immunity of infected dogs, through impairing lymphoproliferation and microbicidal mechanisms. This study examined heme oxygenase-1 (HO-1) and its metabolites, oxidative stress and IL-10 levels in CVL and investigated correlations between these parameters. Additionally, the effects of HO-1 inhibition on the lymphoproliferative response and cytokine production in lymph node cells (LNCs) from infected dogs were evaluated. Forty-four dogs, 24 controls and 20 dogs with CVL were selected. Plasma and splenic levels of HO-1, haptoglobin, soluble CD163 receptor, ferritin and IL-10 were determined using capture ELISA. The HO-1 levels and relative gene expression in peripheral blood and bone marrow mononuclear cells were also determined. LNCs proliferation was evaluated with an HO-1 activator and with an HO-1 inhibitor, in the presence of the Leishmania infantum soluble antigen (SAgL), using flow cytometry. HO-1, IL-2, IFN-gamma and IL-10 were also determined in these cultures using capture ELISA. Infected dogs presented oxidative stress and increased HO-1 levels and relative gene expression, with correlation between oxidative stress and HO-1. The substances from heme metabolism and IL-10 were also elevated in the plasma and spleens of infected dogs. IL-10 and HO-1 levels were positively correlated with one another. Inhibition of HO-1 increased LNCs proliferation and decreased IL-10 and IL-2 production in the presence of SAgL. The increased HO-1 metabolism observed in CVL is probably associated with oxidative stress and increased IL-10, which could be one of the mechanisms responsible for inhibition of the lymphoproliferative response in sick dogs.

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“…The mRNA levels of heat shock protein 70 (HSP70), Ki67, IFN-γ, and granzyme B were analysed as previously described [48]. Briefly, total cellular RNA was isolated (RNeasy Mini Kit; Qiagen, Hilden, Germany), and cDNA was amplified using the High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Darmstadt, Germany).…”

Section: Real-time Pcr Detection Of Hsp70 Ki67 Ifn-γ and Granzyme mentioning

confidence: 99%

High-intensity interval training in allogeneic adoptive T-cell immunotherapy – a big HIT?

et al. 2020

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Background: Adoptive transfer of virus-specific T cells (VSTs) represents a prophylactic and curative approach for opportunistic viral infections and reactivations after transplantation. However, inadequate frequencies of circulating memory VSTs in the T-cell donor's peripheral blood often result in insufficient enrichment efficiency and purity of the final T-cell product, limiting the effectiveness of this approach. Methods: This pilot study was designed as a cross-over trial and compared the effect of a single bout (30 min) of high-intensity interval training (HIT) with that of 30 min of continuous exercise (CONT) on the frequency and function of circulating donor VSTs. To this end, we used established immunoassays to examine the donors' cellular immune status, in particular, with respect to the frequency and specific characteristics of VSTs restricted against Cytomegalovirus (CMV)-, Epstein-Barr-Virus (EBV)-and Adenovirus (AdV)-derived antigens. T-cell function, phenotype, activation and proliferation were examined at different time points before and after exercise to identify the most suitable time for T-cell donation. The clinical applicability was determined by small-scale T-cell enrichment using interferon-(IFN-) γ cytokine secretion assay and virus-derived overlapping peptide pools. Results: HIT proved to be the most effective exercise program with up to fivefold higher VST response. In general, donors with a moderate fitness level had higher starting and post-exercise frequencies of VSTs than highly fit donors, who showed significantly lower post-exercise increases in VST frequencies. Both exercise programs boosted the number of VSTs against less immunodominant antigens, specifically CMV (IE-1), EBV (EBNA-1) and AdV (Hexon, Penton), compared to VSTs against immunodominant antigens with higher memory T-cell frequencies. Conclusion: This study demonstrates that exercise before T-cell donation has a beneficial effect on the donor's cellular immunity with respect to the proportion of circulating functionally active VSTs. We conclude that a single bout of HIT exercise 24 h before T-cell donation can significantly improve manufacturing of clinically applicable VSTs. This simple and economical adjuvant treatment proved to be especially efficient in enhancing virus-specific memory T cells with low precursor frequencies.

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Modulation of heme oxygenase-1 by metalloporphyrins increases anti-viral T cell responses

Cited by 15 publications

References 52 publications

Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

The effects of increased heme oxygenase-1 on the lymphoproliferative response in dogs with visceral leishmaniasis

High-intensity interval training in allogeneic adoptive T-cell immunotherapy – a big HIT?

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