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Article ; Online: BCL6 deletion in CD4 T cells does not affect Th2 effector mediated immunity in the skin.

Chandler, Jodie / Prout, Melanie / Old, Sam / Morgan, Cynthia / Ronchese, Franca / Benoist, Christophe / Le Gros, Graham

Immunology and cell biology

2022 Volume 100, Issue 10, Page(s) 791–804

Abstract: Recent studies propose that T follicular helper (Tfh) cells possess a high degree of functional plasticity in addition to their well-defined roles in mediating interleukin-4-dependent switching of germinal center B cells to the production of ... ...

Abstract	Recent studies propose that T follicular helper (Tfh) cells possess a high degree of functional plasticity in addition to their well-defined roles in mediating interleukin-4-dependent switching of germinal center B cells to the production of immunoglobulin (Ig)G1 and IgE antibodies. In particular Tfh cells have been proposed to be an essential stage in Th2 effector cell development that are able to contribute to innate type 2 responses. We used CD4-cre targeted deletion of BCL6 to identify the contribution Tfh cells make to tissue Th2 effector responses in models of atopic skin disease and lung immunity to parasites. Ablation of Tfh cells did not impair the development or recruitment of Th2 effector subsets to the skin and did not alter the transcriptional expression profile or functional activities of the resulting tissue resident Th2 effector cells. However, the accumulation of Th2 effector cells in lung Th2 responses was partially affected by BCL6 deficiency. These data indicate that the development of Th2 effector cells does not require a BCL6 dependent step, implying Tfh and Th2 effector populations follow separate developmental trajectories and Tfh cells do not contribute to type 2 responses in the skin.
MeSH term(s)	CD4-Positive T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Cell Differentiation ; Germinal Center ; B-Lymphocytes ; Proto-Oncogene Proteins c-bcl-6/genetics
Chemical Substances	Proto-Oncogene Proteins c-bcl-6
Language	English
Publishing date	2022-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12589
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Article: Annotated mitochondrial genome with Nanopore R9 signal for

Chandler, Jodie / Camberis, Mali / Bouchery, Tiffany / Blaxter, Mark / Le Gros, Graham / Eccles, David A

F1000Research

2017 Volume 6, Page(s) 56

Abstract: Nippostrongylus ... ...

Abstract	Nippostrongylus brasiliensis
Language	English
Publishing date	2017-01-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2699932-8
ISSN	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.10545.1
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Article ; Online: Gut CD4

Kiner, Evgeny / Willie, Elijah / Vijaykumar, Brinda / Chowdhary, Kaitavjeet / Schmutz, Hugo / Chandler, Jodie / Schnell, Alexandra / Thakore, Pratiksha I / LeGros, Graham / Mostafavi, Sara / Mathis, Diane / Benoist, Christophe

Nature immunology

2021 Volume 22, Issue 2, Page(s) 216–228

Abstract: ... ...

Abstract	CD4
MeSH term(s)	Animals ; Bacteria/immunology ; Bacteria/pathogenicity ; Bacterial Infections/genetics ; Bacterial Infections/immunology ; Bacterial Infections/metabolism ; Bacterial Infections/microbiology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/microbiology ; CD4-Positive T-Lymphocytes/parasitology ; Chromatin/genetics ; Chromatin/metabolism ; Citrobacter rodentium/immunology ; Citrobacter rodentium/pathogenicity ; Colon/immunology ; Colon/metabolism ; Colon/microbiology ; Colon/parasitology ; Cytokines/genetics ; Cytokines/metabolism ; Disease Models, Animal ; Gastrointestinal Microbiome ; Gene Expression Profiling ; Heligmosomatoidea/immunology ; Heligmosomatoidea/pathogenicity ; Host-Pathogen Interactions ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/metabolism ; Intestinal Diseases, Parasitic/genetics ; Intestinal Diseases, Parasitic/immunology ; Intestinal Diseases, Parasitic/metabolism ; Intestinal Diseases, Parasitic/parasitology ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Nematospiroides dubius/immunology ; Nematospiroides dubius/pathogenicity ; Nippostrongylus/immunology ; Nippostrongylus/pathogenicity ; Phenotype ; Salmonella enterica/immunology ; Salmonella enterica/pathogenicity ; Single-Cell Analysis ; Transcription Factor AP-1/genetics ; Transcription Factor AP-1/metabolism ; Transcriptome ; Mice
Chemical Substances	Chromatin ; Cytokines ; Interferon Regulatory Factors ; Transcription Factor AP-1
Language	English
Publishing date	2021-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-020-00836-7
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Article ; Online: Publisher Correction: Gut CD4

Nature immunology

2021 Volume 22, Issue 5, Page(s) 666–668

Language	English
Publishing date	2021-02-25
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-021-00916-2
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Article ; Online: De novo assembly of the complex genome of Nippostrongylus brasiliensis using MinION long reads.

Eccles, David / Chandler, Jodie / Camberis, Mali / Henrissat, Bernard / Koren, Sergey / Le Gros, Graham / Ewbank, Jonathan J

BMC biology

2018 Volume 16, Issue 1, Page(s) 6

Abstract: Background: Eukaryotic genome assembly remains a challenge in part due to the prevalence of complex DNA repeats. This is a particularly acute problem for holocentric nematodes because of the large number of satellite DNA sequences found throughout their ...

Abstract	Background: Eukaryotic genome assembly remains a challenge in part due to the prevalence of complex DNA repeats. This is a particularly acute problem for holocentric nematodes because of the large number of satellite DNA sequences found throughout their genomes. These have been recalcitrant to most genome sequencing methods. At the same time, many nematodes are parasites and some represent a serious threat to human health. There is a pressing need for better molecular characterization of animal and plant parasitic nematodes. The advent of long-read DNA sequencing methods offers the promise of resolving complex genomes. Results: Using Nippostrongylus brasiliensis as a test case, applying improved base-calling algorithms and assembly methods, we demonstrate the feasibility of de novo genome assembly matching current community standards using only MinION long reads. In doing so, we uncovered an unexpected diversity of very long and complex DNA sequences repeated throughout the N. brasiliensis genome, including massive tandem repeats of tRNA genes. Conclusion: Base-calling and assembly methods have improved sufficiently that de novo genome assembly of large complex genomes is possible using only long reads. The method has the added advantage of preserving haplotypic variants and so has the potential to be used in population analyses.
MeSH term(s)	Animals ; Base Sequence/genetics ; Female ; Genome, Helminth/genetics ; High-Throughput Nucleotide Sequencing/methods ; Nippostrongylus/genetics ; Nippostrongylus/isolation & purification ; Rats ; Rats, Inbred Lew ; Rats, Sprague-Dawley ; Sequence Analysis, DNA/methods
Language	English
Publishing date	2018-01-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2133020-7
ISSN	1741-7007 ; 1741-7007
ISSN (online)	1741-7007
ISSN	1741-7007
DOI	10.1186/s12915-017-0473-4
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Article ; Online: Intestinal helminth infection promotes IL-5- and CD4

Filbey, Kara J / Camberis, Mali / Chandler, Jodie / Turner, Rufus / Kettle, Anthony J / Eichenberger, Ramon M / Giacomin, Paul / Le Gros, Graham

Mucosal immunology

2018 Volume 12, Issue 2, Page(s) 352–362

Abstract: The ability of helminths to manipulate the immune system of their hosts to ensure their own survival is often credited with affecting responses to other pathogens. We undertook co-infection experiments in mice to determine how infection with the ... ...

Abstract	The ability of helminths to manipulate the immune system of their hosts to ensure their own survival is often credited with affecting responses to other pathogens. We undertook co-infection experiments in mice to determine how infection with the intestinal helminth Heligmosomoides polygyrus affected the parasitological, immunological and physiological outcomes of a primary infection with a distinct species of helminth; the lung migratory parasite Nippostrongylus brasiliensis. We found that migrating N. brasiliensis larvae were killed in the lungs of H. polygyrus-infected mice by a process involving IL-33-activated CD4
MeSH term(s)	Animals ; Antigens, Helminth/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cell Movement ; Cells, Cultured ; Coinfection ; Cytotoxicity, Immunologic ; Eosinophils/immunology ; Female ; Host-Parasite Interactions ; Immunity ; Interleukin-33/metabolism ; Interleukin-5/metabolism ; Lung/immunology ; Lung/parasitology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nematospiroides dubius/physiology ; Nippostrongylus/physiology ; Strongylida Infections/immunology ; Trichuriasis/immunology ; Trichuris/physiology
Chemical Substances	Antigens, Helminth ; Interleukin-33 ; Interleukin-5
Language	English
Publishing date	2018-11-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2411370-0
ISSN	1935-3456 ; 1933-0219
ISSN (online)	1935-3456
ISSN	1933-0219
DOI	10.1038/s41385-018-0102-8
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Article ; Online: The Basoph8 Mice Enable an Unbiased Detection and a Conditional Depletion of Basophils.

Pellefigues, Christophe / Mehta, Palak / Prout, Melanie Sarah / Naidoo, Karmella / Yumnam, Bibek / Chandler, Jodie / Chappell, Sally / Filbey, Kara / Camberis, Mali / Le Gros, Graham

Frontiers in immunology

2019 Volume 10, Page(s) 2143

Abstract: Basophils are granulocytes involved in parasite immunity and allergic diseases, known for their potent secretion of type 2 cytokines. Identifying their functions has proven to be controversial due to their relative rarity and their complex lineage ... ...

Abstract	Basophils are granulocytes involved in parasite immunity and allergic diseases, known for their potent secretion of type 2 cytokines. Identifying their functions has proven to be controversial due to their relative rarity and their complex lineage phenotype. Here, we show that the expression of basophils lineage markers CD200R3 and FcεRIα is highly variable in inflammatory settings and hinders basophils identification by flow cytometry across multiple disease states or tissues. Fluorophore-conjugated antibody staining of these lineage markers strongly activates basophil type 2 cytokine expression, and represents a potential bias for coculture or
MeSH term(s)	Animals ; Basophils/immunology ; Hypersensitivity/immunology ; Inflammation/immunology ; Mice, Inbred C57BL ; Skin/immunology
Language	English
Publishing date	2019-09-10
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.2019.02143
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Article ; Online: Author Correction: Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote T

Mayer, Johannes U / Hilligan, Kerry L / Chandler, Jodie S / Eccles, David A / Old, Samuel I / Domingues, Rita G / Yang, Jianping / Webb, Greta R / Munoz-Erazo, Luis / Hyde, Evelyn J / Wakelin, Kirsty A / Tang, Shiau-Choot / Chappell, Sally C / von Daake, Sventja / Brombacher, Frank / Mackay, Charles R / Sher, Alan / Tussiwand, Roxane / Connor, Lisa M /

Gallego-Ortega, David / Jankovic, Dragana / Le Gros, Graham / Hepworth, Matthew R / Lamiable, Olivier / Ronchese, Franca

Nature immunology

2022 Volume 23, Issue 6, Page(s) 985

Language	English
Publishing date	2022-04-13
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-022-01203-4
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Article ; Online: A novel blood-feeding detoxification pathway in Nippostrongylus brasiliensis L3 reveals a potential checkpoint for arresting hookworm development.

Bouchery, Tiffany / Filbey, Kara / Shepherd, Amy / Chandler, Jodie / Patel, Deepa / Schmidt, Alfonso / Camberis, Mali / Peignier, Adeline / Smith, Adam A T / Johnston, Karen / Painter, Gavin / Pearson, Mark / Giacomin, Paul / Loukas, Alex / Bottazzi, Maria-Elena / Hotez, Peter / LeGros, Graham

PLoS pathogens

2018 Volume 14, Issue 3, Page(s) e1006931

Abstract: As part of on-going efforts to control hookworm infection, the "human hookworm vaccine initiative" has recognised blood feeding as a feasible therapeutic target for inducing immunity against hookworm infection. To this end, molecular approaches have been ...

Abstract	As part of on-going efforts to control hookworm infection, the "human hookworm vaccine initiative" has recognised blood feeding as a feasible therapeutic target for inducing immunity against hookworm infection. To this end, molecular approaches have been used to identify candidate targets, such as Necator americanus (Na) haemoglobinase aspartic protease-1 (APR-1), with immunogenicity profiled in canine and hamster models. We sought to accelerate the immune analysis of these identified therapeutic targets by developing an appropriate mouse model. Here we demonstrate that Nippostrongylus brasiliensis (Nb), a phylogenetically distant strongylid nematode of rodents, begins blood feeding early in its development and that immunisation with Na-APR-1 can block its growth and completion of its life cycle. Furthermore, we identify a new haem detoxification pathway in Nb required for blood feeding that can be blocked by drugs of the quinolone family, reducing both infection burden and the associated anaemia in rodents. Collectively, our findings show that haem metabolism has potential as a checkpoint for interrupting hookworm development in early stages of the hookworm life cycle and that the Nippostrongylus brasiliensis rodent model is relevant for identifying novel therapeutic targets against human hookworm.
MeSH term(s)	Ancylostomatoidea/drug effects ; Ancylostomatoidea/growth & development ; Animals ; Antibodies, Helminth/pharmacology ; Antigens, Helminth/immunology ; Aspartic Acid Endopeptidases/antagonists & inhibitors ; Aspartic Acid Endopeptidases/immunology ; Erythrocytes/drug effects ; Erythrocytes/parasitology ; Female ; Hookworm Infections/parasitology ; Hookworm Infections/prevention & control ; Life Cycle Stages ; Male ; Mice ; Mice, Inbred C57BL ; Necator americanus/enzymology ; Nippostrongylus/drug effects ; Nippostrongylus/growth & development ; Strongylida Infections/parasitology ; Strongylida Infections/prevention & control
Chemical Substances	Antibodies, Helminth ; Antigens, Helminth ; Aspartic Acid Endopeptidases (EC 3.4.23.-) ; aspartic proteinase-I (EC 3.4.23.-)
Language	English
Publishing date	2018
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.1006931
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Article ; Online: Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote T

Gallego-Ortega, David / Jankovic, Dragana / Le Gros, Graham / Hepworth, Matthew R / Lamiable, Olivier / Ronchese, Franca

Nature immunology

2021 Volume 22, Issue 12, Page(s) 1538–1550

Abstract: The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of ... ...

Abstract	The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11b
MeSH term(s)	Allergens/pharmacology ; Animals ; CD11b Antigen/genetics ; CD11b Antigen/metabolism ; Cell Communication ; Cell Differentiation ; Cells, Cultured ; Databases, Genetic ; Humans ; Interleukin-13/genetics ; Interleukin-13/metabolism ; Langerhans Cells/drug effects ; Langerhans Cells/immunology ; Langerhans Cells/metabolism ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; STAT6 Transcription Factor/genetics ; STAT6 Transcription Factor/metabolism ; Signal Transduction ; Skin/cytology ; Skin/drug effects ; Skin/immunology ; Skin/metabolism ; Th17 Cells/drug effects ; Th17 Cells/immunology ; Th17 Cells/metabolism ; Th2 Cells/drug effects ; Th2 Cells/immunology ; Th2 Cells/metabolism ; Transcriptome ; Mice
Chemical Substances	Allergens ; CD11b Antigen ; IL13 protein, human ; ITGAM protein, human ; Interleukin-13 ; Itgam protein, mouse ; STAT6 Transcription Factor ; STAT6 protein, human ; Stat6 protein, mouse
Language	English
Publishing date	2021-11-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-021-01067-0
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