The goal of this clinical trial is to examine immune responses to the BCG vaccine in healthy adults who have, or who have not, taken antibiotics to deplete their gut bacteria prior to vaccination.
The main question it aims to answer is: does depletion of the gut microbiota lead to impaired BCG-induced protection against specific and non-specific to challenges to the immune system?

开始日期2023-11-23

申办/合作机构

South Australian Health & Medical Research Institute Ltd.

[+5]

100 项与 Centenary Institute of Cancer Medicine and Cell Biology 相关的临床结果

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0 项与 Centenary Institute of Cancer Medicine and Cell Biology 相关的专利（医药）

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449

项与 Centenary Institute of Cancer Medicine and Cell Biology 相关的文献（医药）

2024-12-31·OncoImmunology

MHCII restriction demonstrates B cells have very limited capacity to activate tumour-specific CD4 ⁺ T cells in vivo

Article

作者: Terry, Alexandra M ; Fazekas de St Groth, Barbara ; Guy, Thomas V ; McGuire, Helen M ; Shklovskaya, Elena

There has been growing interest in the role of B cells in antitumour immunity and potential use in adoptive cellular therapies. To date, the success of such therapies is limited. The intrinsic capacity of B cells to specifically activate tumour-specific CD4+ T cells in vivo via TCR-dependent interactions remains poorly defined. We have developed an in vivo tumour model that utilizes MHCII I-E restriction which limits antigen presentation to tumour-specific CD4 T cells to either tumour-specific B cells or host myeloid antigen presenting cells (APCs) in lymphopenic RAG-/-mice. We have previously shown that these naive tumour-specific CD4+ T cells can successfully eradicate established tumours in this model when activated by host APCs. When naïve tumour-specific B cells are the only source of I-E+ APC, very limited proliferation of naïve CD4+ T cells is observed, whereas host I-E+ APCs are potent T cell activators. B cells pre-activated with an anti-CD40 agonistic antibody in vivo support increased T cell proliferation, although far less than host APCs. CD4+ T cells that have already differentiated to an effector/central memory phenotype proliferate more readily in response to naïve B cells, although still 100-fold less than in response to host APCs. This study demonstrates that even in a significantly lymphopenic environment, myeloid APCs are the dominant primary activators of tumour-specific T cells, in contrast to the very limited capacity of tumour-specific B cells. This suggests that future anti-tumour therapies that incorporate activated B cells should also include mechanisms that activate host APCs.

2023-12-01·Clinical Nutrition ESPEN

Central obesity is detrimental to anti-inflammatory, phenotype, and exhaustion markers in mononuclear cells - A cross-sectional study

Article

作者: Rosa-Neto, José Cesar ; Peres, Alessandra ; Figueiredo, Caique ; Dorneles, Gilson Pires ; Romão, Pedro ; Krüger, Karsten ; Dos Santos, Vanessa Ribeiro ; Marmett, Bruna ; Jabur Ribeiro, José Procópio ; Olean-Oliveira, André ; Olean-Oliveira, Tiago ; Lira, Fábio Santos ; Teixeira, Marcos F S ; Abílio de Souza Teixeira, Alexandre ; Padilha, Camila S ; Seraphim, Patrícia M

OBJECTIVETo investigate the role of central obesity on immunometabolic response in peripheral blood mononuclear cells (PBMCs) from normal weight and overweight/obese young men.METHODSEighteen individuals were classified as normal weight (NW; n = 9 - age: 25 ± 5 and BMI: 21.4 ± 1.7) and overweight/obese (OW; n = 9 - age: 29 ± 7 and BMI: 29.2 ± 2.7). The body composition was evaluated by dual-energy x-ray absorptiometry (DXA), waist circumference, and visceral and subcutaneous fat depots by ultrasound. Physical activity levels, metabolic parameters, immune phenotypic characterization, cytokine production by lipopolysaccharide (LPS) -stimulated whole blood cells and LPS or phorbol 12-myristate 13-acetate (PMA)-stimulated PBMC, and mitochondrial respiration in PBMCs were evaluated. Expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPAR-γ), nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR-4), hypoxia-inducible factor-1 alpha (HIF-1α), and adrenergic receptor beta 1 and 2 (AR-β1 and β2) genes were evaluated in cultured PBMC using quantitative real-time polymerase chain reaction (qRT-PCR).RESULTSIndividuals with overweight/obese (OW) presented higher glucose (P = 0.009) and leptin (P = 0.010) than individuals with normal weight (NW). PBMCs of OW under stimulation with LPS presented a lower production of interleukin-10 (IL-10) (P = 0.011) and macrophage inflammatory protein-1alpha (MIP-1α) (P = 0.048) than NW. Mitochondrial respiration rates were not different between NW and OW subjects. Cultured PBMCs in LPS-stimulated condition indicated higher gene expression of AR-β2 in OW, while PMA-stimulated PBMCs presented lower expression of AMPK (P = 0.002) and higher expression of NF-κB (P=<0.0001) than NW. OW presented higher numbers of CD3⁺CD4⁺ T cells (P = 0.009) and higher expression of programmed cell death protein 1 (PD-1) in CD8⁺ T cells (P = 0.001) than NW.CONCLUSIONCentral obesity promoted reductions in interleukin 10 production response and increase in AR-β2 expressions in mitogen-stimulated PBMCs. Furthermore, central obesity altered the phenotype of PBMCs, also increasing the expression of PD-1 exhaustion markers in young adults.

2022-04-01·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease2区 · 生物学

Deletion of kif3a in CK19 positive cells leads to primary cilia loss, biliary cell proliferation and cystic liver lesions in TAA-treated mice

2区 · 生物学

Article

作者: McCaughan, Geoffrey W ; Cheng, Ngan Ching ; Ferreira-Gonzalez, Sofia ; Chen, Jinbiao ; Liu, Ken ; Boland, Jade A ; Forbes, Stuart J ; Watkins, D Neil ; Kench, James G

BACKGROUND & AIMSLoss of primary cilia in epithelial cells is known to cause cystic diseases of the liver and kidney. We have previously shown that during experimental and human cirrhosis that primary cilia were predominantly expressed on biliary cells in the ductular reaction. However, the role of primary cilia in the pathogenesis of the ductular reaction is not fully understood.METHODSPrimary cilia were specifically removed in biliary epithelial cells (BECs) by the administration of tamoxifen to Kif3a^f/f;CK19^CreERT mice at week 2 of a 20-week course of TAA treatment. Biliary progenitor cells were isolated and grown as organoids from gallbladders. Cells and tissue were analysed using histology, immunohistochemistry and Western blot assays.RESULTSAt the end of 20 weeks TAA administration, primary cilia loss in liver BECs resulted in multiple microscopic cystic lesions within an unaltered ductular reaction. These were not seen in control mice who did not receive TAA. There was no effect of biliary primary cilia loss on the development of cirrhosis. Increased cellular proliferation was seen within the cystic structures associated with a decrease in hepatocyte lobular proliferation. Loss of primary cilia within biliary organoids was initially associated with reduced cell passage survival but this inhibitory effect was diminished in later passages. ERK but not WNT signalling was enhanced in primary cilia loss-induced cystic lesions in vivo and its inhibition reduced the expansion of primary cilia deficient biliary progenitor cells in vitro.CONCLUSIONSTAA-treated kif3a BEC-specific knockout mice had an unaltered progression to cirrhosis, but developed cystic lesions that showed increased proliferation.

100 项与 Centenary Institute of Cancer Medicine and Cell Biology 相关的药物交易

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100 项与 Centenary Institute of Cancer Medicine and Cell Biology 相关的转化医学

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