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Article ; Online: Role of T Cells in Chikungunya Virus Infection and Utilizing Their Potential in Anti-Viral Immunity.

Poh, Chek Meng / Chan, Yi-Hao / Ng, Lisa F P

2020 Volume 11, Page(s) 287

Abstract: Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes hallmark debilitating polyarthralgia, fever, and rash in patients. T cell-mediated immunity, especially ... ...

Abstract	Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes hallmark debilitating polyarthralgia, fever, and rash in patients. T cell-mediated immunity, especially CD4
MeSH term(s)	Animals ; Arthralgia ; Chikungunya Fever/immunology ; Chikungunya virus/physiology ; Disease Progression ; Exanthema ; Humans ; Immunologic Memory ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes/immunology
Language	English
Publishing date	2020-02-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00287
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The trinity of COVID-19

Tay, Matthew Zirui / Poh, Chek Meng / Rénia, Laurent / MacAry, Paul A. / Ng, Lisa F. P.

Nature Reviews Immunology

immunity, inflammation and intervention

2020 Volume 20, Issue 6, Page(s) 363–374

Keywords	Immunology ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-020-0311-8
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Zs.A 5565: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The trinity of COVID-19: immunity, inflammation and intervention.

Tay, Matthew Zirui / Poh, Chek Meng / Rénia, Laurent / MacAry, Paul A / Ng, Lisa F P

Nature reviews. Immunology

2020 Volume 20, Issue 6, Page(s) 363–374

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.
MeSH term(s)	Animals ; Betacoronavirus/immunology ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/immunology ; Coronavirus Infections/physiopathology ; Coronavirus Infections/therapy ; Coronavirus Infections/virology ; Disease Progression ; Humans ; Inflammation/etiology ; Inflammation/immunology ; Pandemics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/physiopathology ; Pneumonia, Viral/therapy ; Pneumonia, Viral/virology ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-04-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-020-0311-8
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Zs.A 5565: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Heterosubtypic Protection Induced by a Live Attenuated Influenza Virus Vaccine Expressing Galactose-α-1,3-Galactose Epitopes in Infected Cells.

Yan, Li-Meng / Lau, Sylvia P N / Poh, Chek Meng / Chan, Vera S F / Chan, Michael C W / Peiris, Malik / Poon, Leo L M

mBio

2020 Volume 11, Issue 2

Abstract: Anti-galactose-α-1,3-galactose (anti-α-Gal) antibody is naturally expressed at a high level in humans. It constitutes about 1% of immunoglobulins found in human blood. Here, we designed a live attenuated influenza virus vaccine that can generate α-Gal ... ...

Abstract	Anti-galactose-α-1,3-galactose (anti-α-Gal) antibody is naturally expressed at a high level in humans. It constitutes about 1% of immunoglobulins found in human blood. Here, we designed a live attenuated influenza virus vaccine that can generate α-Gal epitopes in infected cells in order to facilitate opsonization of infected cells, thereby enhancing vaccine-induced immune responses. In the presence of normal human sera, cells infected with this mutant can enhance phagocytosis of human macrophages and cytotoxicity of NK cells
MeSH term(s)	Animals ; Cross Reactions/immunology ; Epitopes/immunology ; Galactose/immunology ; Humans ; Immunogenicity, Vaccine ; Influenza A virus/classification ; Influenza A virus/immunology ; Influenza Vaccines/genetics ; Influenza Vaccines/immunology ; Killer Cells, Natural/immunology ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Orthomyxoviridae Infections/prevention & control ; Vaccines, Attenuated/genetics ; Vaccines, Attenuated/immunology
Chemical Substances	Epitopes ; Influenza Vaccines ; Vaccines, Attenuated ; Galactose (X2RN3Q8DNE)
Language	English
Publishing date	2020-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00027-20
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Article ; Online: Activated Brain Endothelial Cells Cross-Present Malaria Antigen.

Shanshan W Howland / Chek Meng Poh / Laurent Rénia

PLoS Pathogens, Vol 11, Iss 6, p e

2015 Volume 1004963

Abstract: In the murine model of cerebral malaria caused by P. berghei ANKA (PbA), parasite-specific CD8+ T cells directly induce pathology and have long been hypothesized to kill brain endothelial cells that have internalized PbA antigen. We previously reported ... ...

Abstract	In the murine model of cerebral malaria caused by P. berghei ANKA (PbA), parasite-specific CD8+ T cells directly induce pathology and have long been hypothesized to kill brain endothelial cells that have internalized PbA antigen. We previously reported that brain microvessel fragments from infected mice cross-present PbA epitopes, using reporter cells transduced with epitope-specific T cell receptors. Here, we confirm that endothelial cells are the population responsible for cross-presentation in vivo, not pericytes or microglia. PbA antigen cross-presentation by primary brain endothelial cells in vitro confers susceptibility to killing by CD8+ T cells from infected mice. IFNγ stimulation is required for brain endothelial cross-presentation in vivo and in vitro, which occurs by a proteasome- and TAP-dependent mechanism. Parasite strains that do not induce cerebral malaria were phagocytosed and cross-presented less efficiently than PbA in vitro. The main source of antigen appears to be free merozoites, which were avidly phagocytosed. A human brain endothelial cell line also phagocytosed P. falciparum merozoites. Besides being the first demonstration of cross-presentation by brain endothelial cells, our results suggest that interfering with merozoite phagocytosis or antigen processing may be effective strategies for cerebral malaria intervention.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2015-06-01T00:00:00Z
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: Activated Brain Endothelial Cells Cross-Present Malaria Antigen.

Howland, Shanshan W / Poh, Chek Meng / Rénia, Laurent

PLoS pathogens

2015 Volume 11, Issue 6, Page(s) e1004963

Abstract	In the murine model of cerebral malaria caused by P. berghei ANKA (PbA), parasite-specific CD8+ T cells directly induce pathology and have long been hypothesized to kill brain endothelial cells that have internalized PbA antigen. We previously reported that brain microvessel fragments from infected mice cross-present PbA epitopes, using reporter cells transduced with epitope-specific T cell receptors. Here, we confirm that endothelial cells are the population responsible for cross-presentation in vivo, not pericytes or microglia. PbA antigen cross-presentation by primary brain endothelial cells in vitro confers susceptibility to killing by CD8+ T cells from infected mice. IFNγ stimulation is required for brain endothelial cross-presentation in vivo and in vitro, which occurs by a proteasome- and TAP-dependent mechanism. Parasite strains that do not induce cerebral malaria were phagocytosed and cross-presented less efficiently than PbA in vitro. The main source of antigen appears to be free merozoites, which were avidly phagocytosed. A human brain endothelial cell line also phagocytosed P. falciparum merozoites. Besides being the first demonstration of cross-presentation by brain endothelial cells, our results suggest that interfering with merozoite phagocytosis or antigen processing may be effective strategies for cerebral malaria intervention.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Antigens, Protozoan/immunology ; Brain/immunology ; Brain/parasitology ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Cross-Priming/immunology ; Disease Models, Animal ; Endothelial Cells/immunology ; Fluorescent Antibody Technique ; Humans ; Malaria, Cerebral/immunology ; Mice ; Mice, Inbred C57BL
Chemical Substances	Antigens, Protozoan
Language	English
Publishing date	2015-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7366
ISSN (online)	1553-7374
ISSN	1553-7366
DOI	10.1371/journal.ppat.1004963
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Multiplex Screening Assay for Identifying Cytotoxic CD8

Poh, Chek Meng / Zheng, Jian / Channappanavar, Rudragouda / Chang, Zi Wei / Nguyen, Thi H O / Rénia, Laurent / Kedzierska, Katherine / Perlman, Stanley / Poon, Leo L M

Frontiers in immunology

2020 Volume 11, Page(s) 400

Abstract: The cytotoxicity of epitope-specific ... ...

Abstract	The cytotoxicity of epitope-specific CD8
MeSH term(s)	Animals ; Epitopes, T-Lymphocyte/immunology ; Epitopes, T-Lymphocyte/isolation & purification ; Flow Cytometry/methods ; Humans ; Mice ; Staining and Labeling/methods ; T-Lymphocytes, Cytotoxic/immunology
Chemical Substances	Epitopes, T-Lymphocyte
Keywords	covid19
Language	English
Publishing date	2020-03-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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.2020.00400
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Article: The trinity of COVID-19: immunity, inflammation and intervention

Tay, Matthew Zirui / Poh, Chek Meng / Rénia, Laurent / MacAry, Paul A / Ng, Lisa F P

Nat. rev. immunol

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32346093
Database	COVID19

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Article ; Online: Combined use of live-attenuated and inactivated influenza vaccines to enhance heterosubtypic protection.

Yan, Li-Meng / Li, Olive T W / Poh, Chek M / Perera, Ranawaka A P M / Valkenburg, Sophie A / Peiris, Malik / Poon, Leo L M

Virology

2018 Volume 525, Page(s) 73–82

Abstract: The limited protection of current commerical vaccines necessitates the investigation of novel vaccine strategies for unpredictable outbreaks. To investigate the feasibility of using vaccines derived from Group 1 influenza A virus to induce broadly cross- ... ...

Abstract	The limited protection of current commerical vaccines necessitates the investigation of novel vaccine strategies for unpredictable outbreaks. To investigate the feasibility of using vaccines derived from Group 1 influenza A virus to induce broadly cross-reactive immune responses against multiple influenza subtypes, we tested a panel of sequential 4-dose immunization regimens in mice. Mice were treated with inactivated (seasonal H1N1, pandemic H1N1 and H5N1) and vaccinia virus-based H5N1 live-attenuated vaccines in different combinations. Mice were then challenged by viruses of either Group 1 (H1N1) or Group 2 (H3N2, H7N7) influenza virus. All studied sequential 4-dose vaccinations could induce some degrees of heterosubtypic protection in mice. Amongst all these regimens, the combined use of inactivated and live-attenuated vaccines could achieve the best heterologous protection. These results highlight the synergistic effect of combining different vaccine platforms to enhance heterosubtypic protection against influenza viruses.
MeSH term(s)	Animals ; Antigens, Viral ; Female ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections/prevention & control ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology ; Vaccines, Inactivated/administration & dosage ; Vaccines, Inactivated/immunology
Chemical Substances	Antigens, Viral ; Influenza Vaccines ; Vaccines, Attenuated ; Vaccines, Inactivated
Language	English
Publishing date	2018-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2018.09.007
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Article ; Online: Interferon regulatory factor 1 is essential for pathogenic CD8+ T cell migration and retention in the brain during experimental cerebral malaria.

Gun, Sin Yee / Claser, Carla / Teo, Teck Hui / Howland, Shanshan W / Poh, Chek Meng / Chye, Rebecca Ren Ying / Ng, Lisa F P / Rénia, Laurent

Cellular microbiology

2018 Volume 20, Issue 5, Page(s) e12819

Abstract: Host immune response has a key role in controlling the progression of malaria infection. In the well-established murine model of experimental cerebral malaria (ECM) with Plasmodium berghei ANKA infection, proinflammatory Th1 and CD8+ T cell response are ... ...

Abstract	Host immune response has a key role in controlling the progression of malaria infection. In the well-established murine model of experimental cerebral malaria (ECM) with Plasmodium berghei ANKA infection, proinflammatory Th1 and CD8+ T cell response are essential for disease development. Interferon regulatory factor 1 (IRF1) is a transcription factor that promotes Th1 responses, and its absence was previously shown to protect from ECM death. Yet the exact mechanism of protection remains unknown. Here we demonstrated that IRF1-deficient mice (IRF1 knockout) were protected from ECM death despite displaying early neurological signs. Resistance to ECM death was a result of reduced parasite sequestration and pathogenic CD8+ T cells in the brain. Further analysis revealed that IRF1 deficiency suppress interferon-γ production and delayed CD8+ T cell proliferation. CXCR3 expression was found to be decreased in pathogenic CD8+ T cells, which limited their migration to the brain. In addition, reduced expression of adhesion molecules by brain endothelial cells hampered leucocyte retention in the brain. Taken together, these factors limited sequestration of pathogenic CD8+ T cells and consequently its ability to induce extensive damage to the blood-brain barrier.
MeSH term(s)	Animals ; Brain/microbiology ; Brain/pathology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/microbiology ; Cell Movement/genetics ; Disease Models, Animal ; Gene Expression Regulation ; Humans ; Interferon Regulatory Factor-1/genetics ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Malaria, Cerebral/genetics ; Malaria, Cerebral/immunology ; Malaria, Cerebral/microbiology ; Mice ; Mice, Knockout ; Plasmodium berghei/pathogenicity ; Receptors, CXCR3/genetics
Chemical Substances	Cxcr3 protein, mouse ; Interferon Regulatory Factor-1 ; Irf1 protein, mouse ; Receptors, CXCR3
Language	English
Publishing date	2018-01-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1468320-9
ISSN	1462-5822 ; 1462-5814
ISSN (online)	1462-5822
ISSN	1462-5814
DOI	10.1111/cmi.12819
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