human dendritic cells
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Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 164
Author(s):  
Hannah K. Fitzgerald ◽  
Sinead A. O’Rourke ◽  
Eva Desmond ◽  
Nuno G. B. Neto ◽  
Michael G. Monaghan ◽  
...  

The extracellular parasite and causative agent of African sleeping sickness Trypanosoma brucei (T. brucei) has evolved a number of strategies to avoid immune detection in the host. One recently described mechanism involves the conversion of host-derived amino acids to aromatic ketoacids, which are detected at relatively high concentrations in the bloodstream of infected individuals. These ketoacids have been shown to directly suppress inflammatory responses in murine immune cells, as well as acting as potent inducers of the stress response enzyme, heme oxygenase 1 (HO-1), which has proven anti-inflammatory properties. The aim of this study was to investigate the immunomodulatory properties of the T. brucei-derived ketoacids in primary human immune cells and further examine their potential as a therapy for inflammatory diseases. We report that the T. brucei-derived ketoacids, indole pyruvate (IP) and hydroxyphenylpyruvate (HPP), induce HO-1 expression through Nrf2 activation in human dendritic cells (DC). They also limit DC maturation and suppress the production of pro-inflammatory cytokines, which, in turn, leads to a reduced capacity to differentiate adaptive CD4+ T cells. Furthermore, the ketoacids are capable of modulating DC cellular metabolism and suppressing the inflammatory profile of cells isolated from patients with inflammatory bowel disease. This study therefore not only provides further evidence of the immune-evasion mechanisms employed by T. brucei, but also supports further exploration of this new class of HO-1 inducers as potential therapeutics for the treatment of inflammatory conditions.


Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 92
Author(s):  
Astrid Strack ◽  
Andrea Deinzer ◽  
Christian Thirion ◽  
Silke Schrödel ◽  
Jan Dörrie ◽  
...  

Due to their ability to trigger strong immune responses, adenoviruses (HAdVs) in general and the serotype5 (HAdV-5) in particular are amongst the most popular viral vectors in research and clinical application. However, efficient transduction using HAdV-5 is predominantly achieved in coxsackie and adenovirus receptor (CAR)-positive cells. In the present study, we used the transduction enhancer LentiBOOST® comprising the polycationic Polybrene to overcome these limitations. Using LentiBOOST®/Polybrene, we yielded transduction rates higher than 50% in murine bone marrow-derived dendritic cells (BMDCs), while maintaining their cytokine expression profile and their capability to induce T-cell proliferation. In human dendritic cells (DCs), we increased the transduction rate from 22% in immature (i)DCs or 43% in mature (m)DCs to more than 80%, without inducing cytotoxicity. While expression of specific maturation markers was slightly upregulated using LentiBOOST®/Polybrene on iDCs, no effect on mDC phenotype or function was observed. Moreover, we achieved efficient HAdV5 transduction also in human monocytes and were able to subsequently differentiate them into proper iDCs and functional mDCs. In summary, we introduce LentiBOOST® comprising Polybrene as a highly potent adenoviral transduction agent for new in-vitro applications in a set of different immune cells in both mice and humans.


2022 ◽  
Vol 06 (01) ◽  
Author(s):  
Kuprianov Victor ◽  
Lyudmila Nikolaeva ◽  
Anna Zykova ◽  
Anna Dedova ◽  
Artemiy Vakhrameev ◽  
...  

Nano Letters ◽  
2021 ◽  
Author(s):  
Linyan Nie ◽  
Anggrek C. Nusantara ◽  
Viraj G. Damle ◽  
Maxim V. Baranov ◽  
Mayeul Chipaux ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3279
Author(s):  
Dante Barreda ◽  
César Santiago ◽  
Juan R. Rodríguez ◽  
José F. Rodríguez ◽  
José M. Casasnovas ◽  
...  

Dendritic cells (DCs) are the most potent antigen-presenting cells, and their function is essential to configure adaptative immunity and avoid excessive inflammation. DCs are predicted to play a crucial role in the clinical evolution of the infection by the severe acute respiratory syndrome (SARS) coronavirus (CoV)-2. DCs interaction with the SARS-CoV-2 Spike protein, which mediates cell receptor binding and subsequent fusion of the viral particle with host cell, is a key step to induce effective immunity against this virus and in the S protein-based vaccination protocols. Here we evaluated human DCs in response to SARS-CoV-2 S protein, or to a fragment encompassing the receptor binding domain (RBD) challenge. Both proteins increased the expression of maturation markers, including MHC molecules and costimulatory receptors. DCs interaction with the SARS-CoV-2 S protein promotes activation of key signaling molecules involved in inflammation, including MAPK, AKT, STAT1, and NFκB, which correlates with the expression and secretion of distinctive proinflammatory cytokines. Differences in the expression of ACE2 along the differentiation of human monocytes to mature DCs and inter-donor were found. Our results show that SARS-CoV-2 S protein promotes inflammatory response and provides molecular links between individual variations and the degree of response against this virus.


mBio ◽  
2021 ◽  
Author(s):  
Anupama Karnam ◽  
Srinivasa Reddy Bonam ◽  
Naresh Rambabu ◽  
Sarah Sze Wah Wong ◽  
Vishukumar Aimanianda ◽  
...  

The balance between effector CD4 + T-cell and immunosuppressive regulatory T-cell (Treg) responses determines the outcome of an infectious disease. The signaling pathways that regulate human CD4 + T-effector versus Treg responses to the fungi are not completely understood.


BioMetals ◽  
2021 ◽  
Author(s):  
Yi Jia ◽  
Liangliang Zhang ◽  
Xianmei Liu ◽  
Shichao Zhang ◽  
Jie Dai ◽  
...  

Author(s):  
Elżbieta Rutkowska ◽  
Iwona Kwiecień ◽  
Rafał Sokołowski ◽  
Joanna Bednarek ◽  
Agata Raniszewska ◽  
...  

2021 ◽  
Vol 16 (10) ◽  
pp. 4855-4877
Author(s):  
Marcela Alcántara-Hernández ◽  
Juliana Idoyaga

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1098
Author(s):  
Ananta Prasad Arukha ◽  
Christian Furlan Freguia ◽  
Meerambika Mishra ◽  
Jyoti K. Jha ◽  
Subhashinie Kariyawasam ◽  
...  

Inflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation comprised of Crohn’s disease and ulcerative colitis. Centers for Disease Control and Prevention report that 1.3% of the population of the United States (approximately 3 million people) were affected by the disease in 2015, and the number keeps increasing over time. IBD has a multifactorial etiology, from genetic to environmental factors. Most of the IBD treatments revolve around disease management, by reducing the inflammatory signals. We previously identified the surface layer protein A (SlpA) of Lactobacillus acidophilus that possesses anti-inflammatory properties to mitigate murine colitis. Herein, we expressed SlpA in a clinically relevant, food-grade Lactococcus lactis to further investigate and characterize the protective mechanisms of the actions of SlpA. Oral administration of SlpA-expressing L. lactis (R110) mitigated the symptoms of murine colitis. Oral delivery of R110 resulted in a higher expression of IL-27 by myeloid cells, with a synchronous increase in IL-10 and cMAF in T cells. Consistent with murine studies, human dendritic cells exposed to R110 showed exquisite differential gene regulation, including IL-27 transcription, suggesting a shared mechanism between the two species, hence positioning R110 as potentially effective at treating colitis in humans.


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