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Book ; Online: Immunity to Malaria and Vaccine Strategies

Couper, Kevin N. / Hafalla, Julius C. / Butler, Noah S. / Haque, Ashraful

2019

Keywords	Medicine ; Immunology ; Malaria ; Plasmodium ; Vaccination ; T cells ; B cells ; Dendritic Cells
Size	1 electronic resource (487 pages)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021230095
ISBN	9782889630462 ; 2889630463
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: The NLRP3 inflammasome as a target for sensorineural hearing loss.

Gregory, Grace E / Munro, Kevin J / Couper, Kevin N / Pathmanaban, Omar N / Brough, David

Clinical immunology (Orlando, Fla.)

2023 Volume 249, Page(s) 109287

Abstract: Sensorineural hearing loss is the most common type of hearing loss in adults and occurs due to damage of the inner ear caused by a range of factors including ageing, excessive noise, toxins, and cancer. Auto-inflammatory disease is also a cause of ... ...

Abstract	Sensorineural hearing loss is the most common type of hearing loss in adults and occurs due to damage of the inner ear caused by a range of factors including ageing, excessive noise, toxins, and cancer. Auto-inflammatory disease is also a cause of hearing loss and there is evidence that inflammation could contribute to hearing loss in other conditions. Within the inner ear there are resident macrophage cells that respond to insults and whose activation correlates with damage. The NLRP3 inflammasome is a multi-molecular pro-inflammatory protein complex that forms in activated macrophages and may contribute to hearing loss. The aim of this article is to discuss the evidence for the NLRP3 inflammasome and associated cytokines as potential therapeutic targets for sensorineural hearing loss in conditions ranging from auto-inflammatory disease to tumour-induced hearing loss in vestibular schwannoma.
MeSH term(s)	Adult ; Humans ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Hearing Loss, Sensorineural/etiology ; Hearing Loss, Sensorineural/metabolism ; Ear, Inner/metabolism ; Hearing Loss/complications
Chemical Substances	Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein
Language	English
Publishing date	2023-03-11
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2023.109287
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Plasmodium falciparum-infected erythrocyte co-culture with the monocyte cell line THP-1 does not trigger production of soluble factors reducing brain microvascular barrier function.

Storm, Janet / Camarda, Grazia / Haley, Michael J / Brough, David / Couper, Kevin N / Craig, Alister G

PloS one

2023 Volume 18, Issue 5, Page(s) e0285323

Abstract: Monocytes contribute to the pro-inflammatory immune response during the blood stage of a Plasmodium falciparum infection, but their precise role in malaria pathology is not clear. Besides phagocytosis, monocytes are activated by products from P. ... ...

Abstract	Monocytes contribute to the pro-inflammatory immune response during the blood stage of a Plasmodium falciparum infection, but their precise role in malaria pathology is not clear. Besides phagocytosis, monocytes are activated by products from P. falciparum infected erythrocytes (IE) and one of the activation pathways is potentially the NLR family pyrin domain containing 3 (NLRP3) inflammasome, a multi-protein complex that leads to the production of interleukin (IL)-1β. In cerebral malaria cases, monocytes accumulate at IE sequestration sites in the brain microvascular and the locally produced IL-1β, or other secreted molecules, could contribute to leakage of the blood-brain barrier. To study the activation of monocytes by IE within the brain microvasculature in an in vitro model, we co-cultured IT4var14 IE and the monocyte cell line THP-1 for 24 hours and determined whether generated soluble molecules affect barrier function of human brain microvascular endothelial cells, measured by real time trans-endothelial electrical resistance. The medium produced after co-culture did not affect endothelial barrier function and similarly no effect was measured after inducing oxidative stress by adding xanthine oxidase to the co-culture. While IL-1β does decrease barrier function, barely any IL-1β was produced in the co- cultures, indicative of a lack of or incomplete THP-1 activation by IE in this co-culture model.
MeSH term(s)	Humans ; Plasmodium falciparum ; Monocytes/metabolism ; Coculture Techniques ; Endothelial Cells/metabolism ; Malaria, Falciparum ; Inflammasomes/metabolism ; Erythrocytes/metabolism ; Cell Line ; Brain/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Interleukin-1beta/metabolism
Chemical Substances	Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Interleukin-1beta
Language	English
Publishing date	2023-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0285323
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Evaluation of 4-Aminoquinoline Hydrazone Analogues as Potential Leads for Drug-Resistant Malaria.

Magwaza, Rachael N / Abubaker, Muna / Hussain, Buthaina / Haley, Michael / Couper, Kevin / Freeman, Sally / Nirmalan, Niroshini J

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 18

Abstract: The emergence of resistance to first-line antimalarial drugs calls for the development of new therapies for drug-resistant malaria. The efficacy of quinoline-based antimalarial drugs has prompted the development of novel quinolines. A panel of 4- ... ...

Abstract	The emergence of resistance to first-line antimalarial drugs calls for the development of new therapies for drug-resistant malaria. The efficacy of quinoline-based antimalarial drugs has prompted the development of novel quinolines. A panel of 4-aminoquinoline hydrazone analogues were tested on the multidrug-resistant K1 strain of
MeSH term(s)	Animals ; Mice ; Antimalarials/pharmacology ; Malaria/drug therapy ; Aminoquinolines ; Malaria, Falciparum/drug therapy ; Plasmodium falciparum
Chemical Substances	Antimalarials ; 4-aminoquinoline (GTE5P5L97N) ; Aminoquinolines
Language	English
Publishing date	2023-09-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28186471
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The comparable tumour microenvironment in sporadic and

Gregory, Grace E / Jones, Adam Paul / Haley, Michael J / Hoyle, Christopher / Zeef, Leo A H / Lin, I-Hsuan / Coope, David J / King, Andrew T / Evans, D Gareth / Paszek, Pawel / Couper, Kevin N / Brough, David / Pathmanaban, Omar N

Brain communications

2023 Volume 5, Issue 4, Page(s) fcad197

Abstract: Bilateral vestibular schwannoma is the hallmark ... ...

Abstract	Bilateral vestibular schwannoma is the hallmark of
Language	English
Publishing date	2023-07-21
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcad197
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Plasmodium falciparum-infected erythrocyte co-culture with the monocyte cell line THP-1 does not trigger production of soluble factors reducing brain microvascular barrier function.

Janet Storm / Grazia Camarda / Michael J Haley / David Brough / Kevin N Couper / Alister G Craig

PLoS ONE, Vol 18, Iss 5, p e

2023 Volume 0285323

Abstract	Monocytes contribute to the pro-inflammatory immune response during the blood stage of a Plasmodium falciparum infection, but their precise role in malaria pathology is not clear. Besides phagocytosis, monocytes are activated by products from P. falciparum infected erythrocytes (IE) and one of the activation pathways is potentially the NLR family pyrin domain containing 3 (NLRP3) inflammasome, a multi-protein complex that leads to the production of interleukin (IL)-1β. In cerebral malaria cases, monocytes accumulate at IE sequestration sites in the brain microvascular and the locally produced IL-1β, or other secreted molecules, could contribute to leakage of the blood-brain barrier. To study the activation of monocytes by IE within the brain microvasculature in an in vitro model, we co-cultured IT4var14 IE and the monocyte cell line THP-1 for 24 hours and determined whether generated soluble molecules affect barrier function of human brain microvascular endothelial cells, measured by real time trans-endothelial electrical resistance. The medium produced after co-culture did not affect endothelial barrier function and similarly no effect was measured after inducing oxidative stress by adding xanthine oxidase to the co-culture. While IL-1β does decrease barrier function, barely any IL-1β was produced in the co- cultures, indicative of a lack of or incomplete THP-1 activation by IE in this co-culture model.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evaluation of 4-Aminoquinoline Hydrazone Analogues as Potential Leads for Drug-Resistant Malaria

Rachael N. Magwaza / Muna Abubaker / Buthaina Hussain / Michael Haley / Kevin Couper / Sally Freeman / Niroshini J. Nirmalan

Molecules, Vol 28, Iss 6471, p

2023 Volume 6471

Abstract	The emergence of resistance to first-line antimalarial drugs calls for the development of new therapies for drug-resistant malaria. The efficacy of quinoline-based antimalarial drugs has prompted the development of novel quinolines. A panel of 4-aminoquinoline hydrazone analogues were tested on the multidrug-resistant K1 strain of Plasmodium falciparum : IC 50 values after a 48 h cycle ranged from 0.60 to 49 µM, while the 72 h cycle ranged from 0.026 to 0.219 μM. Time-course assays were carried out to define the activity of the lead compounds, which inhibited over 50% growth in 24 h and 90% growth in 72 h. Cytotoxicity assays with HepG2 cells showed IC 50 values of 0.87–11.1 μM, whereas in MDBK cells, IC 50 values ranged from 1.66 to 11.7 μM. High selectivity indices were observed for the lead compounds screened at 72 h on P. falciparum . Analyses of stage specificity revealed that the ring stages of the parasite life cycle were most affected. Based on antimalarial efficacy and in vitro safety profiles, lead compound 4-(2-benzylidenehydrazinyl)-6-methoxy-2-methylquinoline 2 was progressed to drug combination studies for the detection of synergism, with a combinatory index of 0.599 at IC 90 for the combination with artemether, indicating a synergistic antimalarial activity. Compound 2 was screened on different strains of P. falciparum (3D7, Dd2), which maintained similar activity to K1, suggesting no cross-resistance between multidrug resistance and sensitive parasite strains. In vivo analysis with 2 showed the suppression of parasitaemia with P. yoelii NL (non-lethal)-treated mice (20 mg/kg and 5 mg/kg).
Keywords	4-aminoquinoline ; hydrazone ; antimalarial ; NQO2 inhibitors ; antimalarial drug interaction ; SAR ; Organic chemistry ; QD241-441
Subject code	572 ; 500
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Essential Role Played by B Cells in Supporting Protective Immunity Against

Sahputra, Rinal / Ruckerl, Dominik / Couper, Kevin N / Muller, Werner / Else, Kathryn J

Frontiers in immunology

2019 Volume 10, Page(s) 2842

Abstract: How B cells contribute to protective immunity against parasitic nematodes remains unclear, with their importance as accessory cells underexplored. In this study, anti-CD20 monoclonal antibody (α-CD20 mAb)-mediated depletion of B cells from C57BL/6 mice ... ...

Abstract	How B cells contribute to protective immunity against parasitic nematodes remains unclear, with their importance as accessory cells underexplored. In this study, anti-CD20 monoclonal antibody (α-CD20 mAb)-mediated depletion of B cells from C57BL/6 mice revealed an important role for B cells in supporting Th2 immune responses and thus expulsion of
MeSH term(s)	Animals ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Biomarkers ; Cytokines/biosynthesis ; Flow Cytometry ; Gene Expression Regulation ; Genetic Background ; Host-Parasite Interactions/genetics ; Host-Parasite Interactions/immunology ; Immunohistochemistry ; Male ; Mice ; Single-Cell Analysis ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; Trichuriasis/immunology ; Trichuriasis/parasitology ; Trichuris/immunology
Chemical Substances	Biomarkers ; Cytokines
Language	English
Publishing date	2019-12-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.02842
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Treatment with specific and pan-plasma membrane calcium ATPase (PMCA) inhibitors reduces malaria parasite growth in vitro and in vivo.

Asih, Puji B S / Siregar, Josephine E / Dewayanti, Farahana K / Pravitasari, Normalita E / Rozi, Ismail E / Rizki, Andita F M / Risandi, Rifqi / Couper, Kevin N / Oceandy, Delvac / Syafruddin, Din

Malaria journal

2022 Volume 21, Issue 1, Page(s) 206

Abstract: Background: Rapid emergence of Plasmodium resistance to anti-malarial drug mainstays has driven a continual effort to discover novel drugs that target different biochemical pathway (s) during infection. Plasma membrane Calcium + 2 ATPase (PMCA4), a ... ...

Abstract	Background: Rapid emergence of Plasmodium resistance to anti-malarial drug mainstays has driven a continual effort to discover novel drugs that target different biochemical pathway (s) during infection. Plasma membrane Calcium + 2 ATPase (PMCA4), a novel plasma membrane protein that regulates Calcium levels in various cells, namely red blood cell (RBC), endothelial cell and platelets, represents a new biochemical pathway that may interfere with susceptibility to malaria and/or severe malaria. Methods: This study identified several pharmacological inhibitors of PMCA4, namely ATA and Resveratrol, and tested for their anti-malarial activities in vitro and in vivo using the Plasmodium falciparum 3D7 strain, the Plasmodium berghei ANKA strain, and Plasmodium yoelii 17XL strain as model. Results: In vitro propagation of P. falciparum 3D7 strain in the presence of a wide concentration range of the inhibitors revealed that the parasite growth was inhibited in a dose-dependent manner, with IC Results: The results confirmed that both compounds exhibit moderate to potent anti-malarial activities with the strongest parasite growth inhibition shown by resveratrol at 0.231 µM. In vivo models using P. berghei ANKA for experimental cerebral malaria and P. yoelii 17XL for the effect on parasite growth, showed that the highest dose of ATA, 30 mg/kg BW, increased survival of the mice. Likewise, resveratrol inhibited the parasite growth following 4 days intraperitoneal injection at the dose of 100 mg/kg BW. Conclusion: The findings indicate that the PMCA4 of the human host may be a potential target for novel anti-malarials, either as single drug or in combination with the currently available effective anti-malarials.
MeSH term(s)	Animals ; Antimalarials ; Calcium/pharmacology ; Malaria, Cerebral ; Mice ; Parasites ; Plasma Membrane Calcium-Transporting ATPases ; Plasmodium berghei ; Plasmodium falciparum ; Resveratrol/pharmacology
Chemical Substances	Antimalarials ; Plasma Membrane Calcium-Transporting ATPases (EC 3.6.3.8) ; Resveratrol (Q369O8926L) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-06-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2091229-8
ISSN	1475-2875 ; 1475-2875
ISSN (online)	1475-2875
ISSN	1475-2875
DOI	10.1186/s12936-022-04228-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Memory CD8

Shaw, Tovah N / Haley, Michael J / Dookie, Rebecca S / Godfrey, Jenna J / Cheeseman, Antonn J / Strangward, Patrick / Zeef, Leo A H / Villegas-Mendez, Ana / Couper, Kevin N

Immunology

2021 Volume 164, Issue 4, Page(s) 737–753

Abstract: Experimental cerebral malaria (ECM) is a severe complication of Plasmodium berghei ANKA (PbA) infection in mice, characterized by ... ...

Abstract	Experimental cerebral malaria (ECM) is a severe complication of Plasmodium berghei ANKA (PbA) infection in mice, characterized by CD8
MeSH term(s)	Animals ; Biomarkers ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/pathology ; Chemotaxis, Leukocyte/immunology ; Disease Susceptibility ; Epitopes, T-Lymphocyte/immunology ; Erythrocytes/immunology ; Erythrocytes/parasitology ; Extracellular Matrix ; Host-Parasite Interactions/immunology ; Immunologic Memory ; Immunophenotyping ; Life Cycle Stages ; Lymphocyte Activation/immunology ; Malaria/immunology ; Malaria/metabolism ; Malaria/parasitology ; Malaria/pathology ; Malaria, Cerebral/immunology ; Malaria, Cerebral/metabolism ; Malaria, Cerebral/parasitology ; Mice ; Mice, Transgenic ; Organ Specificity/immunology ; Plasmodium berghei/physiology
Chemical Substances	Biomarkers ; Epitopes, T-Lymphocyte
Language	English
Publishing date	2021-08-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.13405
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Ud II Zs.181: Show issues

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