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1. The Trypanosoma Brucei KIFC1 Kinesin Ensures the Fast Antibody Clearance Required for Parasite Infectivity

Author

Lecordier, Laurence, Uzureau, Sophie, Vanwalleghem, Gilles, Deleu, Magali, Crowet, Jean-Marc, Barry, Paul, Moran, Barry, Voorheis, Paul, Dumitru, Andra-Cristina, Yamaryo-Botté, Yoshiki, Dieu, Marc, Tebabi, Patricia, Vanhollebeke, Benoit, Lins, Laurence, Botté, Cyrille Y., Alsteens, David, Dufrêne, Yves, Pérez-Morga, David, Nolan, Derek P., and Pays, Etienne

Published
2020
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5. Endocytosis in African Trypanosomes

Author

Nolan, Derek P., Garcia-Salcedo, Jose A., Geuskens, Maurice, Salmon, Didier, Paturiaux-Hanocq, Françoise, Pays, Annette, Tebabi, Patricia, Pays, Etienne, Black, Samuel J., editor, and Seed, J. Richard, editor

Published
2002
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6. The Trypanosoma brucei-Derived Ketoacids, Indole Pyruvate and Hydroxyphenylpyruvate, Induce HO-1 Expression and Suppress Inflammatory Responses in Human Dendritic Cells

Author

Fitzgerald, Hannah K., primary, O’Rourke, Sinead A., additional, Desmond, Eva, additional, Neto, Nuno G. B., additional, Monaghan, Michael G., additional, Tosetto, Miriam, additional, Doherty, Jayne, additional, Ryan, Elizabeth J., additional, Doherty, Glen A., additional, Nolan, Derek P., additional, Fletcher, Jean M., additional, and Dunne, Aisling, additional

Published
2022
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9. TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei

Author

Shameer, Sanu, Logan-Klumpler, Flora J., Vinson, Florence, Cottret, Ludovic, Merlet, Benjamin, Achcar, Fiona, Boshart, Michael, Berriman, Matthew, Breitling, Rainer, Bringaud, Frédéric, Bütikofer, Peter, Cattanach, Amy M., Bannerman-Chukualim, Bridget, Creek, Darren J., Crouch, Kathryn, de Koning, Harry P., Denise, Hubert, Ebikeme, Charles, Fairlamb, Alan H., Ferguson, Michael A. J., Ginger, Michael L., Hertz-Fowler, Christiane, Kerkhoven, Eduard J., Mäser, Pascal, Michels, Paul A. M., Nayak, Archana, Nes, David W., Nolan, Derek P., Olsen, Christian, Silva-Franco, Fatima, Smith, Terry K., Taylor, Martin C., Tielens, Aloysius G. M., Urbaniak, Michael D., van Hellemond, Jaap J., Vincent, Isabel M., Wilkinson, Shane R., Wyllie, Susan, Opperdoes, Fred R., Barrett, Michael P., and Jourdan, Fabien

Published
2015
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10. Mechanism of Trypanosoma brucei gambiense resistance to human serum

Author

Uzureau, Pierrick, Uzureau, Sophie, Lecordier, Laurence, Fontaine, Frederic, Tebabi, Patricia, Homble, Fabrice, Grelard, Axelle, Zhendre, Vanessa, Nolan, Derek P., Lins, Laurence, Crowet, Jean-Marc, Pays, Annette, Felu, Cecile, Poelvoorde, Philippe, Vanhollebeke, Benoit, Moestrup, Soren K., Lyngso, Jeppe, Pedersen, Jan Skov, Mottram, Jeremy C., Dufoure, Erick J., Perez-Morga, David, and Pays, Etienne

Subjects
Lipid membranes -- Physiological aspects, Serum -- Properties, Trypanosoma brucei -- Properties, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The African parasite Trypanosoma bruceigambiense accounts for 97% of human sleeping sickness cases (1). T. b. gambiense resists the specific human innate immunity acting against several other tsetse-fly-transmitted trypanosome species such as T. b. brucei, the causative agent of nagana disease in cattle. Human immunity to some African trypanosomes is due to two serum complexes designated trypanolytic factors (TLF-1 and -2), which both contain haptoglobin-related protein (HPR) and apolipoprotein LI (APOL1) (2-4). Whereas HPR association with haemoglobin (Hb) allows TLF-1 binding and uptake via the trypanosome receptor TbHpHbR (ref. 5), TLF-2 enters trypanosomes independently of TbHpHbR (refs 4, 5). APOL1 kills trypanosomes after insertion into endosomal/lysosomal membranes (2,6,7). Here we report that T. b. gambiense resists TLFs via a hydrophobic β-sheet of the T. b. gambiense-specific glycoprotein (TgsGP) (8), which prevents APOL1 toxicity and induces stiffening of membranes upon interaction with lipids. Two additional features contribute to resistance to TLFs: reduction of sensitivity to APOL1 requiring cysteine protease activity, and TbHpHbR inactivation due to a L210S substitution. According to such a multifactorial defence mechanism, transgenic expression of T. b. brucei TbHpHbR in T. b. gambiense did not cause parasite lysis in normal human serum. However, these transgenic parasites were killed in hypohaptoglobinaemic serum, after high TLF-1 uptake in the absence of haptoglobin (Hp) that competes for Hb and receptor binding. TbHpHbR inactivation preventing high APOL1 loading in hypohaptoglobinaemic serum may have evolved because of the overlapping endemic area of T.b. gambiense infection and malaria, the main cause of haemolysis-induced hypohaptoglobinaemia in western and central Africa (9)., The protozoan flagellate Trypanosoma brucei brucei infects many mammals, except some primates including humans, where it is lysed by the trypanolytic protein APOL1 (refs 2, 6, 7). APOL1 is associated [...]

Published
2013

13. Apolipoprotein L-I is the trypanosome lytic factor of human serum

Author

Vanhamme, Luc, Paturiaux-Hanocq, Francoise, Poelvoorde, Philippe, Nolan, Derek P., Lins, Laurence, Van Den Abbeele, Jan, Pays, Annette, Tebabi, Patricia, Van Xong, Huang, Jacquet, Alain, Moguilevsky, Nicole, Dieu, Marc, Kane, John P., De Baetselier, Patrick, Brasseur, Robert, and Pays, Etienne

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Luc Vanhamme [1, 2]; Françoise Paturiaux-Hanocq [1, 2]; Philippe Poelvoorde [1, 2]; Derek P. Nolan [1, 3]; Laurence Lins [4]; Jan Van Den Abbeele [5]; Annette Pays [1]; Patricia [...]

Published
2003
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20. TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei

Author

LS Biochemie van parasieten, B&C BRC-SIB-TR, Regenerative Medicine, Stem Cells & Cancer, Shameer, Sanu, Logan-Klumpler, Flora J, Vinson, Florence, Cottret, Ludovic, Merlet, Benjamin, Achcar, Fiona, Boshart, Michael, Berriman, Matthew, Breitling, Rainer, Bringaud, Frédéric, Bütikofer, Peter, Cattanach, Amy M, Bannerman-Chukualim, Bridget, Creek, Darren J, Crouch, Kathryn, de Koning, Harry P, Denise, Hubert, Ebikeme, Charles, Fairlamb, Alan H, Ferguson, Michael A J, Ginger, Michael L, Hertz-Fowler, Christiane, Kerkhoven, Eduard J, Mäser, Pascal, Michels, Paul A M, Nayak, Archana, Nes, David W, Nolan, Derek P, Olsen, Christian, Silva-Franco, Fatima, Smith, Terry K, Taylor, Martin C, Tielens, Aloysius G M, Urbaniak, Michael D, van Hellemond, Jaap J, Vincent, Isabel M, Wilkinson, Shane R, Wyllie, Susan, Opperdoes, Fred R, Barrett, Michael P, Jourdan, Fabien, LS Biochemie van parasieten, B&C BRC-SIB-TR, Regenerative Medicine, Stem Cells & Cancer, Shameer, Sanu, Logan-Klumpler, Flora J, Vinson, Florence, Cottret, Ludovic, Merlet, Benjamin, Achcar, Fiona, Boshart, Michael, Berriman, Matthew, Breitling, Rainer, Bringaud, Frédéric, Bütikofer, Peter, Cattanach, Amy M, Bannerman-Chukualim, Bridget, Creek, Darren J, Crouch, Kathryn, de Koning, Harry P, Denise, Hubert, Ebikeme, Charles, Fairlamb, Alan H, Ferguson, Michael A J, Ginger, Michael L, Hertz-Fowler, Christiane, Kerkhoven, Eduard J, Mäser, Pascal, Michels, Paul A M, Nayak, Archana, Nes, David W, Nolan, Derek P, Olsen, Christian, Silva-Franco, Fatima, Smith, Terry K, Taylor, Martin C, Tielens, Aloysius G M, Urbaniak, Michael D, van Hellemond, Jaap J, Vincent, Isabel M, Wilkinson, Shane R, Wyllie, Susan, Opperdoes, Fred R, Barrett, Michael P, and Jourdan, Fabien

Published
2015

21. TrypanoCyc:a community-led biochemical pathways database for Trypanosoma brucei

Author

Shameer, Sanu, Logan-Klumpler, Flora J., Vinson, Florence, Cottret, Ludovic, Merlet, Benjamin, Achcar, Fiona, Boshart, Michael, Berriman, Matthew, Breitling, Rainer, Bringaud, Frédéric, Bütikofer, Peter, Cattanach, Amy M., Bannerman-Chukualim, Bridget, Creek, Darren J., Crouch, Kathryn, de Koning, Harry P., Denise, Hubert, Ebikeme, Charles, Fairlamb, Alan H., Ferguson, Michael A. J., Ginger, Michael L., Hertz-Fowler, Christiane, Kerkhoven, Eduard J., Mäser, Pascal, Michels, Paul A. M., Nayak, Archana, Nes, David W., Nolan, Derek P., Olsen, Christian, Silva-Franco, Fatima, Smith, Terry K., Taylor, Martin C., Tielens, Aloysius G. M., Urbaniak, Michael D., van Hellemond, Jaap J., Vincent, Isabel M., Wilkinson, Shane R., Wyllie, Susan, Opperdoes, Fred R., Barrett, Michael P., Jourdan, Fabien, Shameer, Sanu, Logan-Klumpler, Flora J., Vinson, Florence, Cottret, Ludovic, Merlet, Benjamin, Achcar, Fiona, Boshart, Michael, Berriman, Matthew, Breitling, Rainer, Bringaud, Frédéric, Bütikofer, Peter, Cattanach, Amy M., Bannerman-Chukualim, Bridget, Creek, Darren J., Crouch, Kathryn, de Koning, Harry P., Denise, Hubert, Ebikeme, Charles, Fairlamb, Alan H., Ferguson, Michael A. J., Ginger, Michael L., Hertz-Fowler, Christiane, Kerkhoven, Eduard J., Mäser, Pascal, Michels, Paul A. M., Nayak, Archana, Nes, David W., Nolan, Derek P., Olsen, Christian, Silva-Franco, Fatima, Smith, Terry K., Taylor, Martin C., Tielens, Aloysius G. M., Urbaniak, Michael D., van Hellemond, Jaap J., Vincent, Isabel M., Wilkinson, Shane R., Wyllie, Susan, Opperdoes, Fred R., Barrett, Michael P., and Jourdan, Fabien

Abstract

The metabolic network of a cell represents the catabolic and anabolic reactions that interconvert small molecules (metabolites) through the activity of enzymes, transporters and non-catalyzed chemical reactions. Our understanding of individual metabolic networks is increasing as we learn more about the enzymes that are active in particular cells under particular conditions and as technologies advance to allow detailed measurements of the cellular metabolome. Metabolic network databases are of increasing importance in allowing us to contextualise data sets emerging from transcriptomic, proteomic and metabolomic experiments. Here we present a dynamic database, TrypanoCyc (http://www.metexplore.fr/trypanocyc/), which describes the generic and condition-specific metabolic network of Trypanosoma brucei, a parasitic protozoan responsible for human and animal African trypanosomiasis. In addition to enabling navigation through the BioCyc-based TrypanoCyc interface, we have also implemented a network-based representation of the information through MetExplore, yielding a novel environment in which to visualise the metabolism of this important parasite.

Published
2015

22. Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1

Author

Vanwalleghem, Gilles, primary, Fontaine, Frédéric, additional, Lecordier, Laurence, additional, Tebabi, Patricia, additional, Klewe, Kristoffer, additional, Nolan, Derek P., additional, Yamaryo-Botté, Yoshiki, additional, Botté, Cyrille, additional, Kremer, Anneke, additional, Burkard, Gabriela Schumann, additional, Rassow, Joachim, additional, Roditi, Isabel, additional, Pérez-Morga, David, additional, and Pays, Etienne, additional

Published
2015
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24. Endocytosis in African Trypanosomes

Author

Nolan, Derek P., primary, Garcia-Salcedo, Jose A., additional, Geuskens, Maurice, additional, Salmon, Didier, additional, Paturiaux-Hanocq, Françoise, additional, Pays, Annette, additional, Tebabi, Patricia, additional, and Pays, Etienne, additional

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25. TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei

Author

Shameer, Sanu, primary, Logan-Klumpler, Flora J., additional, Vinson, Florence, additional, Cottret, Ludovic, additional, Merlet, Benjamin, additional, Achcar, Fiona, additional, Boshart, Michael, additional, Berriman, Matthew, additional, Breitling, Rainer, additional, Bringaud, Frédéric, additional, Bütikofer, Peter, additional, Cattanach, Amy M., additional, Bannerman-Chukualim, Bridget, additional, Creek, Darren J., additional, Crouch, Kathryn, additional, de Koning, Harry P., additional, Denise, Hubert, additional, Ebikeme, Charles, additional, Fairlamb, Alan H., additional, Ferguson, Michael A. J., additional, Ginger, Michael L., additional, Hertz-Fowler, Christiane, additional, Kerkhoven, Eduard J., additional, Mäser, Pascal, additional, Michels, Paul A. M., additional, Nayak, Archana, additional, Nes, David W., additional, Nolan, Derek P., additional, Olsen, Christian, additional, Silva-Franco, Fatima, additional, Smith, Terry K., additional, Taylor, Martin C., additional, Tielens, Aloysius G. M., additional, Urbaniak, Michael D., additional, van Hellemond, Jaap J., additional, Vincent, Isabel M., additional, Wilkinson, Shane R., additional, Wyllie, Susan, additional, Opperdoes, Fred R., additional, Barrett, Michael P., additional, and Jourdan, Fabien, additional

Published
2014
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30. The trypanolytic factor of human serum

Author

Pays, Etienne, primary, Vanhollebeke, Benoit, additional, Vanhamme, Luc, additional, Paturiaux-Hanocq, Françoise, additional, Nolan, Derek P., additional, and Pérez-Morga, David, additional

Published
2006
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35. A Role for the Dynamic Acylation of a Cluster of Cysteine Residues in Regulating the Activity of the Glycosylphosphatidylinositol-specific Phospholipase C ofTrypanosoma brucei

Author

Paturiaux-Hanocq, Françoise, primary, Hanocq-Quertier, Jacqueline, additional, de Almeida, Maria Lucia Cardoso, additional, Nolan, Derek P., additional, Pays, Annette, additional, Vanhamme, Luc, additional, Van den Abbeele, Jan, additional, Wasunna, Christine L., additional, Carrington, Mark, additional, and Pays, Etienne, additional

Published
2000
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46. The mitochondrion in bloodstream forms of <em>Trypanosoma brucei</em> is energized by the electrogenic pumping of protons catalysed by the F1F0-ATPase.

Author

Nolan, Derek P. and Voorheis, H. Paul

Subjects
*TRYPANOSOMA brucei, *MITOCHONDRIA, *PROTONS, *ADENOSINE triphosphatase, *CELL membranes, *BIOCHEMISTRY
Abstract

Bloodstream forms of Trypanosoma brucei were found to maintain a significant membrane potential across their mitochondrial inner membrane (ΔΨm) in addition to a plasma membrane potential (ΔΨp). Significantly, the ΔΨm was selectively abolished by low concentrations of specific inhibitors of the F1F0-ATPase, such as oligomycin, whereas inhibition of mitochondrial respiration with salicylhydroxamic acid was without effect. Thus, the mitochondrial membrane potential is generated and maintained exclusively by the electrogenic translocation of H+, catalysed by the mitochondrial F1F0-ATPase at the expense of ATP rather than by the mitochondrial electron-transport chain present in T. brucei. Consequently, bloodstream forms of T. brucei cannot engage in oxidative phosphorylation. The mitochondrial membrane potential generated by the mitochondrial F1F0-ATPase in intact trypanosomes was calculated after solving the two-compartment problem for the uptake of the lipophilic cation, methyltriphenylphosphonium (MePh3P+) and was shown to have a value of approximately 150 mV. When the value for the ΔΨm is combined with that for the mitochondrial pH gradient (Nolan and Voorheis, 1990), the mitochondrial proton-motive force was calculated to be greater than 190 mV. It seems likely that this mitochondrial proton-motive force serves a role in the directional transport of ions and metabolites across the promitochondrial inner membrane during the bloodstream stage of the life cycle, as well as promoting the import of nuclear-encoded protein into the promitochondrion during the transformation of bloodstream forms into the next stage of the life cycle of T. brucei. [ABSTRACT FROM AUTHOR]

Published
1992
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47. The distribution of permeant ions demonstrates the presence of a least two distinct electrical gradients in bloodstream forms of <em>Trypanosoma brucei</em>.

Author

Nolan, Derek P. and Voorheis, H. Paul

Subjects
*TRYPANOSOMA brucei, *ZOOFLAGELLATES, *HYDROPHOBIC surfaces, *ORGANELLES, *CELL membranes, *BIOCHEMISTRY
Abstract

The distribution of 86Rb+ and the radiolabelled lipophilic cation [3H]methyltriphenylphosphonium (Meph3P+) was used to investigate the membrane potentials that exist in bloodstream forms of Trypanosoma brucei. Even after correction for binding to cellular constituents, the accumulation of MePh3P+ was approximately tenfold greater than the accumulation of Rb+ under resting conditions. The addition of low concentrations of carbonylcy-anide p- trinuoromethoxyphenylhydrazone or valinomycin reduced the accumulation of MePh3P+ tenfold without perturbing the accumulation of Rb+. Although selective permeabilization of the plasma membrane abolished the accumulation of Rb+ and caused a substantial decrease in the accumulation of MePh3P+, a significant carbonylcyanide-p-trinuoromethoxyphenylhydrazone-sensitive accumulation of MePh3P+ persisted under these conditions. These data were consistent with the presence of at least two distinct membrane potentials (ΔΨ) in bloodstream forms of T. brucei; a potential across the plasma membrane (ΔΨp) and an additional ΔΨ, generated by the electrogenic movement of H+, across the membrane of an intracellular organelle that possesses no electrical permeability to Rb+ or K+. [ABSTRACT FROM AUTHOR]

Published
1991
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48. The enzymes of the classical pentose phosphate pathway display differential activities in procyclic and bloodstream forms of Trypanosoma brucei

Author

Cronín, Ciaran N., Nolan, Derek P., and Paul Voorheis, H.

Abstract

The specific activities of each of the enzymes of the classical pentose phosphate pathway have been determined in both cultured procyclic and bloodstream forms of Trypanosoma brucei. Both forms contained glucose-6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconolactonase (EC 3.1.1.31), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), ribose-5-phosphate isomerase (EC 5.3.1.6) and transaldolase (EC 2.2.1.2). However, ribulose-5-phosphate 3′-epimerase (EC 5.1.3.1) and transketolase (EC 2.2.1.1) activities were detectable only in procyclic forms. These results clearly demonstrate that both forms of T. bruceican metabolize glucose via the oxidative segment of the classical pentose phosphate pathway in order to produce d-ribose-5-phosphate for the synthesis of nucleic acids and reduced NADP for other synthetic reactions. However, only procyclic forms are capable of using the non-oxidative segment of the classical pentose phosphate pathway to cycle carbon between pentose and hexose phosphates in order to produce d-glyceraldehyde 3-phosphate as a net product of the pathway. Both forms lack the key gluconeogenic enzyme, fructose-bisphosphatase (EC 3.1.3.11). Consequently, neither form should be able to engage in gluconeogenesis nor should procyclic forms be able to return any of the glyceraldehyde 3-phosphate produced in the pentose phosphate pathway to glucose 6-phosphate. This last specific metabolic arrangement and the restriction of all but the terminal steps of glycolysis to the glycosome may be the observations required to explain the presence of distinct cytosolic and glycosomal isoenzymes of glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. These same observations also may provide the basis for explaining the presence of cytosolic hexokinase and phosphoglucose isomerase without the presence of any cytosolic phosphofructokinase activity. The key enzymes of the Entner-Doudoroff pathway, 6-phosphogluconate dehydratase (EC 4.2.1.12) and 2-keto-3-deoxy-6-phosphogluconate aldolase (EC 4.1.2.14) were not detected in either procyclic or bloodstream forms of T. brucei.

Published
1989
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49. Characterization of a Novel, Stage-specific, Invariant Surface Protein in Trypanosoma bruceiContaining an Internal, Serine-rich, Repetitive Motif*

Author

Nolan, Derek P., Jackson, David G., Windle, Henry J., Pays, Annette, Geuskens, Maurice, Michel, Alain, Voorheis, H. Paul, and Pays, Etienne

Abstract

A new surface membrane protein, invariant surface glycoprotein termed ISG100, was identified inTrypanosoma brucei, using catalyzed surface, radioiodination of intact cells. This integral membrane glycoprotein was purified by a combination of detergent extraction, lectin-affinity, and ion-exchange chromatography followed by preparative SDS-polyacrylamide gel electrophoresis. The protein was expressed only in bloodstream forms of the parasite, was heavilyN-glycosylated, and was present in different clonal variants of the same serodeme as well as in different serodemes. The gene for this protein was isolated by screening a cDNA expression library with antibodies against the purified protein followed by screening of a genomic library. The nucleotide sequence of the gene (4050 base pairs) predicted a highly reiterative polypeptide containing three distinct domains, a unique N-terminal domain of about 10 kDa containing three potential N-glycosylation sites, which was followed by a large internal domain consisting entirely of 72 consecutive copies of a serine-rich, 17-amino acid motif (∼113 kDa) and terminated with an apparent transmembrane spanning region of about 3.3 kDa. The internal repeat region of this gene (3672 base pairs) represents the largest reiterative coding sequence to be fully characterized in any species of trypanosome. There was no significant homology with other known proteins, and overall the predicted protein was extremely hydrophobic. Unlike the genes for other surface proteins, the gene encoding ISG100was present as a single copy. Although present in the flagellar pocket, ISG100was predominantly associated with components of the pathways for endo/exocytosis, such as intracellular vesicles located in the proximity of the pocket as well a large, electron-lucent perinuclear digestive vacuole.

Published
1997
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50. The Trypanosoma brucei-derived ketoacids, indole pyruvate and hydroxyphenylpyruvate, induce HO-1 expression and suppress inflammatory responses in human dendritic cells

Author

HRB, Fitzgerald, Hannah K., O'Rourke, Sinead A., Desmond, Eva, Neto, Nuno G.B., Monaghan, Michael G., Tosetto, Miriam, Doherty, Jayne, Ryan, Elizabeth J., Doherty, Glen A., Nolan, Derek P., Fletcher, Jean M., Dunne, Aisling, HRB, Fitzgerald, Hannah K., O'Rourke, Sinead A., Desmond, Eva, Neto, Nuno G.B., Monaghan, Michael G., Tosetto, Miriam, Doherty, Jayne, Ryan, Elizabeth J., Doherty, Glen A., Nolan, Derek P., Fletcher, Jean M., and Dunne, Aisling

Abstract

peer-reviewed, 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.

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