The Experts below are selected from a list of 33534 Experts worldwide ranked by ideXlab platform
David M Schauder - One of the best experts on this subject based on the ideXlab platform.
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pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors
Proceedings of the National Academy of Sciences of the United States of America, 2017Co-Authors: David M Schauder, Weiqing Jing, Aimin Jiang, Nikhil S Joshi, Bryon D JohnsonAbstract:Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a Bacterial Antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice. The dual-specific CD8 T cells expanded vigorously, migrated to tumor sites, and robustly eradicated primary tumors. The mice cured from ReACT also developed immunological memory against tumor rechallenge. Mechanistically, we have found that this combined approach reverts the immunosuppressive TME and recruits CD8 T cells with an increased number and killing ability to the tumors.
Jose M Gonzaleznavajas - One of the best experts on this subject based on the ideXlab platform.
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regulatory t cells restrict permeability to Bacterial Antigen translocation and preserve short chain fatty acids in experimental cirrhosis
Hepatology Communications, 2018Co-Authors: Oriol Juanola, Isabel Gomezhurtado, Pedro Zapater, Jose M Gonzaleznavajas, Paula Pinero, Esther Caparros, Rocio Garciavillalba, Alicia Marin, Fabian Tarin, Francisco A TomasbarberanAbstract:Intestinal permeability to translocation of Bacterial products is increased in cirrhosis. Regulatory T cells (Tregs) remain central to the interplay between the host and microbial milieu. We propose that Tregs are involved in promoting gut barrier integrity and a balanced interaction with gut microbiota–derived short‐chain fatty acids (SCFAs). Carbon tetrachloride cirrhosis was induced in wild‐type and recombination activating gene 1 (Rag1)‐/‐ mice. Naive T cells and Treg cells were transferred into Rag1 ‐/‐ mice. Intestinal permeability was assessed in vivo after lipopolysaccharide (LPS) oral administration, and Bacterial DNA presence was evaluated in mesenteric lymph nodes. Transcript and protein levels of tight‐junction (TJ) proteins were measured in colonic tissue. Intestinal T helper profile in response to Escherichia coli (E. coli) was determined by flow cytometry. SCFAs were measured by gas chromatography–mass spectrometry in colonic content before and after E. coli challenge. Rag1 ‐/‐ mice showed significantly increased permeability to LPS and Bacterial DNA translocation rate compared with control mice. Naive T and Treg cotransfer significantly reduced gut permeability to Bacterial Antigen translocation and restored TJ protein expression in Rag1 ‐/‐ mice. Naive T and Treg replenishment in Rag1 ‐/‐ mice restrained proinflammatory differentiation of intestinal lymphocytes in response to E. coli. The main SCFA concentration resulted in significant reduction in Rag1 ‐/‐ mice after E. coli administration but remained unaltered after naive T and Tregs cotransfer. The reduced expression of SCFA receptors induced by E. coli was reestablished following naive T and Treg reconstitution in Rag1 ‐/‐ mice. Conclusion: The restriction of gut permeability, local inflammatory differentiation, and loss of bacteria‐derived SCFAs foster the value of Tregs in preventing Bacterial translocation in cirrhosis.
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toll like receptor polymorphisms compromise the inflammatory response against Bacterial Antigen translocation in cirrhosis
Scientific Reports, 2017Co-Authors: Paula Pinero, Pedro Zapater, Jose M Gonzaleznavajas, Oriol Juanola, Esther Caparros, Paula Gimenez, Jose Such, Ruben FrancesAbstract:Bacterial translocation is associated with clinically relevant complications in cirrhosis. We evaluated the effect of toll-like receptor polymorphisms in the soluble response against these episodes. Consecutive patients with cirrhosis and ascitic fluid were distributed by TLR2 rs4696480, TLR4 rs4986790, and TLR9 rs187084 single-nucleotide polymorphisms. Lipoteichoic acid, lipopolyssaccharide, Bacterial-DNA, pro-inflammatory cytokines and nitric oxide levels were quantified in serum samples. In vitro response against specific ligands in variant TLR genotypes was evaluated. One hundred and fourteen patients were included. Variant TLR-2, TLR-4 and TLR-9 SNP genotypes were associated with significantly increased serum levels of LTA, LPS and Bacterial-DNA. TNF-α, IL-6 and nitric oxide serum levels were significantly decreased in all variant TLR genotyped patients. Cytokine levels were significantly less upregulated in response to specific TLR-ligands in patients with all variant vs wildtype TLR genotypes. Although in vitro gene expression levels of all wildtype and variant TLRs were similar, MyD88 and NFkB were significantly downregulated in cells from TLR-variant genotyped patients in response to their ligands. Variant TLR genotypes are associated with an increased circulating Antigen burden and a decreased proinflammatory response in cirrhosis. This immunodeficiency may facilitate bacteria-related complications in cirrhosis and enhance TLR targeting for its management.
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protective effect of bifidobacterium pseudocatenulatum cect7765 against induced Bacterial Antigen translocation in experimental cirrhosis
Liver International, 2014Co-Authors: Alba Moratalla, Isabel Gomezhurtado, Arlette Santacruz, Angela Moya, Gloria Peiro, Pedro Zapater, Jose M GonzaleznavajasAbstract:Background & Aims Intervention in the gut ecosystem is considered as a potential strategy to treat liver diseases and their complications. We have evaluated the effects of Bifidobacterium pseudocatenulatum CECT7765 on Bacterial translocation and the liver status in experimental cirrhosis. Animals & Methods Liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at week 12. One week prior to laparotomy, animals received B. pseudocatenulatum CECT7765 (109cfu/daily) or placebo intragastrically. All animals received Escherichia coli (107cfu/single dose) intragastrically 24 hours before laparotomy. A group of naive non-treated animals was included as control. Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected. Liver histology, profibrogenic genes expression, Bacterial DNA translocation, serum endotoxaemia and liver cytokine levels were measured. Results Bifidobacterium pseudocatenulatum CECT7765 showed no significant effect on structural liver damage, as determined by histological evaluation, alpha-smooth muscle actin distribution, profibrogenic gene expression levels, total hydroxyproline levels and malon dialdehyde production compared with mice receiving placebo. Interestingly, Bacterial DNA translocation and serum endotoxin levels were significantly decreased in mice receiving the Bifidobacterium strain compared with placebo. Gut barrier integrity markers were up-regulated in mice receiving B. pseudocatenulatum CECT7765 and quantitatively correlated with intestinal gene copy numbers of the bifidoBacterial strain. Gene expression levels of several anti-inflammatory mediators were also increased in mice receiving B. pseudocatenulatum CECT7765 compared with placebo. Conclusion Oral administration of B. pseudocatenulatum CECT7765 is associated with improved gut barrier integrity and shows a beneficial effect against induced Bacterial Antigen translocation in the CCl4-model of cirrhosis.
Bryon D Johnson - One of the best experts on this subject based on the ideXlab platform.
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pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors
Proceedings of the National Academy of Sciences of the United States of America, 2017Co-Authors: David M Schauder, Weiqing Jing, Aimin Jiang, Nikhil S Joshi, Bryon D JohnsonAbstract:Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a Bacterial Antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice. The dual-specific CD8 T cells expanded vigorously, migrated to tumor sites, and robustly eradicated primary tumors. The mice cured from ReACT also developed immunological memory against tumor rechallenge. Mechanistically, we have found that this combined approach reverts the immunosuppressive TME and recruits CD8 T cells with an increased number and killing ability to the tumors.
E. Abraham - One of the best experts on this subject based on the ideXlab platform.
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Effects of haemorrhage on Bacterial Antigen specific pulmonary plasma cell function
Clinical & Experimental Immunology, 2008Co-Authors: A Robinson, E. AbrahamAbstract:Nosocomial pneumonia is frequent after haemorrhage and trauma, and often contributes to multiple organ system failure, morbidity and mortality in this setting. Although the percentages and numbers of Bacterial polysaccharide Antigen-specific pulmonary B cell clonal precursors are markedly decreased after haemorrhage, the effects of haemorrhage on pulmonary plasma cells actually producing antibody to these Antigens are unknown. To investigate this question, the numbers of intraparenchymal pulmonary plasma cells producing antibody against the Bacterial polysaccharide Antigen levan (from Aerobacter levanicum) as well as Bacterial Antigen specific secretory IgA (sIgA) titres in the lungs were determined at various time points after 30% blood volume haemorrhage. Reduced numbers of Bacterial Antigen specific pulmonary plasma cells were found for more than 21 days following haemorrhage. An almost complete disappearance from the lungs of levan specific plasma cells occurred between 3 and 21 days after blood loss. Titres of Bacterial Antigen specific sIgA in the lungs were decreased starting at 3 days post-haemorrhage and remained significantly depressed for more than 35 days after blood loss. These results demonstrate that haemorrhage produces profound and long-lasting suppression in Bacterial Antigen-specific pulmonary plasma cell function. Because these effects do not occur immediately post-haemorrhage, immunization techniques able to enhance Bacterial Antigen specific sIgA titres at pulmonary surfaces may be able to increase resistance to nosocomial pneumonia if administered shortly after injury and blood loss.
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Effects of hemorrhage and resuscitation on Bacterial Antigen-specific pulmonary plasma cell function
Critical Care Medicine, 1991Co-Authors: Anstella D. Robinson, E. AbrahamAbstract:BACKGROUND AND METHODS Nosocomial pneumonia is frequent after hemorrhage and trauma, and often contributes to multiple organ system failure, morbidity, and mortality in this setting. Although the percentages and numbers of resting pulmonary B cells (clonal precursors) able to be stimulated to produce antibodies to Bacterial Antigens are markedly decreased after hemorrhage, the effects of hemorrhage on the pulmonary plasma cells actually producing antibody to Bacterial Antigens have not been examined. To investigate this question, mice were bled 30% blood volume, then resuscitated with the shed blood 1 hr later. At predetermined times after hemorrhage, the mice were intranasally immunized with liposomes containing the Bacterial polysaccharide Antigen levan (from Aerobacter levanicum). One week later, lung lavages were performed to measure Bacterial Antigen-specific secretory immunoglobulin A (sIgA) titers and the numbers of intraparenchymal pulmonary plasma cells producing antibody against the Bacterial Antigen were determined. RESULTS Reduced numbers of pulmonary plasma cells producing antibody against the immunizing Bacterial polysaccharide Antigen were found between 1 and 14 days after blood loss, and titers of Bacterial Antigen-specific secretory IgA were decreased for greater than 2 wks after hemorrhage. The importance of these abnormalities in pulmonary B-cell function was demonstrated by an increased susceptibility to Pseudomonas aeruginosa pneumonia in mice infected 4 days after hemorrhage, when Bacterial Antigen-specific pulmonary plasma cell numbers were at their lowest point. Resuscitated mice showed the same increased susceptibility to P. aeruginosa pneumonia as did hemorrhaged but unresuscitated animals. CONCLUSIONS Hemorrhage, even if resuscitated, results in alterations in Bacterial Antigen-specific pulmonary B-cell function and secretory IgA production that are profound, long lasting, and associated with increased susceptibility to infection at this mucosal surface. Because these effects on pulmonary B-cell function do not occur immediately after hemorrhage, immunization techniques able to enhance Bacterial Antigen-specific secretory IgA titers at pulmonary surfaces may be able to increase resistance to nosocomial pneumonia if administered shortly after injury and blood loss.
J Heesemann - One of the best experts on this subject based on the ideXlab platform.
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experimental yersinia infection of human synovial cells persistence of live bacteria and generation of Bacterial Antigen deposits including ghosts nucleic acid free Bacterial rods
Infection and Immunity, 1996Co-Authors: H I Huppertz, J HeesemannAbstract:Yersinia enterocolitica O:3 was maintained in primary cultures of human synovial cells for 6 weeks as cultivable organisms and thereafter for 2 more weeks as Antigen aggregates containing specific lipopolysaccharides (LPS). Some seemingly intact bacteria were "ghosts," Bacterial rods possessing LPS but not DNA. The prolonged persistence of yersiniae, and consequently of Yersinia Antigens, in synovial cells may be the cause of the maintenance of the inflammatory host responses in the joints of patients with reactive arthritis due to Yersinia infection.