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Article ; Online: The Ins and Outs of Cerebral Malaria Pathogenesis: Immunopathology, Extracellular Vesicles, Immunometabolism, and Trained Immunity.

Sierro, Frederic / Grau, Georges E R

2019 Volume 10, Page(s) 830

Abstract: Complications from malaria parasite infections still cost the lives of close to half a million people every year. The most severe is cerebral malaria (CM). Employing murine models of CM, autopsy results, ...

Abstract	Complications from malaria parasite infections still cost the lives of close to half a million people every year. The most severe is cerebral malaria (CM). Employing murine models of CM, autopsy results,
MeSH term(s)	Animals ; Cell Communication/immunology ; Extracellular Vesicles/immunology ; Extracellular Vesicles/metabolism ; Humans ; Immunity, Innate ; Immunologic Memory ; Malaria, Cerebral/immunology ; Malaria, Cerebral/metabolism ; Malaria, Cerebral/pathology
Language	English
Publishing date	2019-04-17
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.2019.00830
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Article ; Online: Neutron Capture Enhances Dose and Reduces Cancer Cell Viability in and out of Beam During Helium and Carbon Ion Therapy.

International journal of radiation oncology, biology, physics

2024

Abstract: Purpose: Neutron capture enhanced particle therapy (NCEPT) is a proposed augmentation of charged particle therapy that exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically ... ...

Abstract	Purpose: Neutron capture enhanced particle therapy (NCEPT) is a proposed augmentation of charged particle therapy that exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically targeted radiation dose to cancer cells. This work is the first experimental demonstration of NCEPT, performed using both carbon and helium ion beams with 2 different targeted neutron capture agents (NCAs). Methods and materials: Human glioblastoma cells (T98G) were irradiated by carbon and helium ion beams in the presence of NCAs [ Results: Cells placed inside the treatment volume reached 10% survival by 2 Gy of carbon or 2 to 3 Gy of helium in the presence of NCAs compared with 5 Gy of carbon and 7 Gy of helium with no NCA. Cells placed adjacent to the treatment volume showed a dose-dependent decrease in cell growth when treated with NCAs, reaching 10% survival by 6 Gy of carbon or helium (to the treatment volume), compared with no detectable effect on cells without NCA. The mean thermal neutron fluence at the center of the SOBP was approximately 2.2 × 10 Conclusions: The addition of NCAs to cancer cells during carbon and helium beam irradiation has a measurable effect on cell survival and growth in vitro. Through the capture of internally generated neutrons, NCEPT introduces the concept of a biochemically targeted radiation dose to charged particle therapy. NCEPT enables the established pharmaceuticals and concepts of neutron capture therapy to be applied to a wider range of deeply situated and diffuse tumors, by targeting this dose to microinfiltrates and cells outside of defined treatment regions. These results also demonstrate the potential for NCEPT to provide an increased dose to tumor tissue within the treatment volume, with a reduction in radiation doses to off-target tissue.
Language	English
Publishing date	2024-03-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2024.02.052
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Article ; Online: The liver contains distinct interconnected networks of CX3CR1

English, Kieran / Tan, Sioh Yang / Kwan, Rain / Holz, Lauren E / Sierro, Frederic / McGuffog, Claire / Kaisho, Tsuneyasu / Heath, William R / MacDonald, Kelli Pa / McCaughan, Geoffrey W / Bowen, David G / Bertolino, Patrick

Immunology and cell biology

2022 Volume 100, Issue 6, Page(s) 394–408

Abstract: Portal tracts are key intrahepatic structures where leukocytes accumulate during immune responses. They contain the blood inflow, which includes portal blood from the gut, and lymphatic and biliary outflow of the liver, and as such represent a key ... ...

Abstract	Portal tracts are key intrahepatic structures where leukocytes accumulate during immune responses. They contain the blood inflow, which includes portal blood from the gut, and lymphatic and biliary outflow of the liver, and as such represent a key interface for potential pathogen entry to the liver. Myeloid cells residing in the interstitium of the portal tract might play an important role in the surveillance or prevention of pathogen dissemination; however, the exact composition and localization of this population has not been explored fully. Our in-depth characterization of portal tract myeloid cells revealed that in addition to T lymphocytes, portal tracts contain a heterogeneous population of MHCII
MeSH term(s)	Dendritic Cells ; Liver ; Macrophages
Language	English
Publishing date	2022-06-19
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.12559
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Article ; Online: The water chemistry and microbiome of household wells in Medawachchiya, Sri Lanka, an area with high prevalence of chronic kidney disease of unknown origin (CKDu).

McDonough, Liza K / Meredith, Karina T / Nikagolla, Chandima / Middleton, Ryan J / Tan, Jian K / Ranasinghe, Asanga V / Sierro, Frederic / Banati, Richard B

Scientific reports

2020 Volume 10, Issue 1, Page(s) 18295

Abstract: Chronic kidney disease (CKD) of unknown etiology (CKDu) mostly affects agricultural communities in Central America, South Asia, Africa, but likely also in North America and Australia. One such area with increased CKDu prevalence is the Medawachchiya ... ...

Abstract	Chronic kidney disease (CKD) of unknown etiology (CKDu) mostly affects agricultural communities in Central America, South Asia, Africa, but likely also in North America and Australia. One such area with increased CKDu prevalence is the Medawachchiya District Secretariat Division of the Anuradhapura District in the North Central Province of Sri Lanka. Recent research has focused on the presence of various microbial pathogens in drinking water as potential causal or contributing factors to CKDu, yet no study to date has performed a more comprehensive microbial and water chemistry assessment of household wells used for domestic water supply in areas of high CKDu prevalence. In this study, we describe the chemical composition and total microbial content in 30 domestic household wells in the Medawachchiya District Secretariat Division. While the chemical composition in the tested wells mostly lies within standard drinking water limits, except for high levels of fluoride (F), magnesium (Mg), sodium (Na), chloride (Cl) and calcium (Ca) in some samples, we find a frequent presence of cyanotoxin-producing Microcystis, confirming earlier studies in Sri Lanka. Since the total microbial content of drinking water also directly influences the composition of the human gut microbiome, it can be considered an important determinant of health. Several bacterial phyla were previously reported in the gut microbiome of patients with CKD. Using these bacteria phyla to define operational taxonomic units, we found that these bacteria also occur in the microbiome of the sampled well water. Based on available environmental data, our study demonstrates associations between the abundances of these bacteria with geographical distribution, well water temperature and likely fertilizer use in the local surface water catchment area of the individual household wells. Our results reinforce the recommendation that household wells with stagnant or infrequently used water should be purged prior to use for drinking water, bathing and irrigation. The latter is suggested because of the reported potential accumulation of bacterial toxins by agricultural crops. The observation that bacteria previously found in chronic kidney disease patients are also present in household wells requires a more detailed systematic study of both the human gut and drinking water microbiomes in CKDu patients, in relation to disease prevalence and progression.
MeSH term(s)	Bacteria/classification ; Bacteria/isolation & purification ; Disease Progression ; Drinking Water/analysis ; Drinking Water/chemistry ; Drinking Water/microbiology ; Gastrointestinal Microbiome ; Humans ; Phylogeny ; Prevalence ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/etiology ; Sri Lanka/epidemiology ; Water Microbiology ; Water Pollutants, Chemical/analysis ; Water Wells
Chemical Substances	Drinking Water ; Water Pollutants, Chemical
Language	English
Publishing date	2020-10-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-75336-7
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Article ; Online: Tissue-resident regulatory T cells accumulate at human barrier lymphoid organs.

Hewavisenti, Rehana V / Ferguson, Angela L / Gasparini, Georgia / Ohashi, Tomoki / Braun, Asolina / Watkins, Thomas S / Miles, John J / Elliott, Michael / Sierro, Frederic / Feng, Carl G / Britton, Warwick J / Gebhardt, Thomas / Tangye, Stuart / Palendira, Umaimainthan

Immunology and cell biology

2021 Volume 99, Issue 8, Page(s) 894–906

Abstract: Regulatory T cells (Tregs) play a critical role in immune regulation and peripheral tolerance. While different types of Tregs have been identified in both mice and humans, much of our understanding about how these cells maintain immune homeostasis is ... ...

Abstract	Regulatory T cells (Tregs) play a critical role in immune regulation and peripheral tolerance. While different types of Tregs have been identified in both mice and humans, much of our understanding about how these cells maintain immune homeostasis is derived from animal models. In this study, we examined two distinct human lymphoid organs to understand how repeated exposure to infections at the mucosal surface influences the phenotype and tissue localization of Tregs. We show that while Tregs in both tonsils and spleen express a tissue-resident phenotype, they accumulate in greater numbers in tonsils. Tonsillar-resident Tregs exhibit a highly suppressive phenotype with significantly increased expression of CD39, ICOS and CTLA-4 compared with their counterparts in circulation or in the spleen. Functionally, resident Tregs are able effectively to suppress T cell proliferation. We further demonstrate that tonsillar-resident Tregs share key features of T follicular helper cells. Spatial analysis reveals that the vast majority of resident Tregs are localized at the border of the T-zone and B cell follicle, as well as within the lymphocyte pockets enriched with resident memory T cells. Together our findings suggest that resident Tregs are strategically co-localized to maintain immune homeostasis at sites of recurrent inflammation.
MeSH term(s)	Animals ; B-Lymphocytes ; Humans ; Lymphocyte Activation ; Mice ; Phenotype ; T-Lymphocytes, Regulatory
Language	English
Publishing date	2021-07-27
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.12481
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Article ; Online: A proinflammatory CD4

Sheu, Angela / Chan, Yixian / Ferguson, Angela / Bakhtyari, Mohammad B / Hawke, Wendy / White, Chris / Chan, Yuk Fun / Bertolino, Patrick J / Woon, Heng G / Palendira, Umaimainthan / Sierro, Frederic / Lau, Sue Mei

Diabetologia

2018 Volume 61, Issue 7, Page(s) 1633–1643

Abstract: Aims/hypothesis: Numerous adaptations of the maternal immune system are necessary during pregnancy to maintain immunological tolerance to the semi-allogeneic fetus. Several complications of pregnancy have been associated with dysregulation of these ... ...

Abstract	Aims/hypothesis: Numerous adaptations of the maternal immune system are necessary during pregnancy to maintain immunological tolerance to the semi-allogeneic fetus. Several complications of pregnancy have been associated with dysregulation of these adaptive mechanisms. While gestational diabetes mellitus (GDM) has been associated with upregulation of circulating inflammatory factors linked to innate immunity, polarisation of the adaptive immune system has not been extensively characterised in this condition. We aimed to characterise pro- and anti-inflammatory CD4 Methods: This is a prospective longitudinal case-control study of 55 women with GDM (cases) and 65 women without GDM (controls) at a tertiary maternity hospital. Quantification of proinflammatory (Th17, Th17.1, Th1) and anti-inflammatory (regulatory T cell [Treg]) CD4 Results: Women with GDM had a significantly greater percentage of Th17 (median 2.49% [interquartile range 1.62-4.60] vs 1.85% [1.13-2.98], p = 0.012) and Th17.1 (3.06% [1.30-4.33] vs 1.55% [0.65-3.13], p = 0.006) cells compared with the control group of women without GDM. Women with GDM also had higher proinflammatory cell ratios (Th17:Treg, Th17.1:Treg and Th1:Treg) in pregnancy compared with the control group of women without GDM. In the control group, there was a statistically significant independent association between 1 h glucose levels in the GTT and Th17 cell percentages, and also between 2 h glucose levels and percentage of Th17 cells. The percentage of Th17 cells and the Th17:Treg ratio declined significantly after delivery in women with GDM, whereas this was not the case with the control group of women. Nevertheless, a milder inflammatory phenotype persisted after delivery (higher Th17:Treg ratio) in women with GDM vs women without. Conclusions/interpretation: Dysregulation of adaptive immunity supports a novel paradigm of GDM that extends beyond hyperglycaemia and altered innate immunity.
MeSH term(s)	Adaptive Immunity ; Adult ; Biomarkers/blood ; Blood Glucose/metabolism ; Case-Control Studies ; Diabetes, Gestational/blood ; Diabetes, Gestational/diagnosis ; Diabetes, Gestational/immunology ; Female ; Humans ; Immunity, Innate ; Inflammation/blood ; Inflammation/diagnosis ; Inflammation/immunology ; Longitudinal Studies ; Phenotype ; Pregnancy ; Prospective Studies ; Severity of Illness Index ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism
Chemical Substances	Biomarkers ; Blood Glucose
Language	English
Publishing date	2018-04-24
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-018-4615-1
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Article ; Online: Pulmonary immunization with a recombinant influenza A virus vaccine induces lung-resident CD4

Flórido, Manuela / Muflihah, Heni / Lin, Leon C W / Xia, Yingju / Sierro, Frederic / Palendira, Mainthan / Feng, Carl G / Bertolino, Patrick / Stambas, John / Triccas, James A / Britton, Warwick J

Mucosal immunology

2018 Volume 11, Issue 6, Page(s) 1743–1752

Abstract: The lung is the primary site of infection with the major human pathogen, Mycobacterium tuberculosis. Effective vaccines against M. tuberculosis must stimulate memory T cells to provide early protection in the lung. Recently, tissue-resident memory T ... ...

Abstract	The lung is the primary site of infection with the major human pathogen, Mycobacterium tuberculosis. Effective vaccines against M. tuberculosis must stimulate memory T cells to provide early protection in the lung. Recently, tissue-resident memory T cells (T
MeSH term(s)	Animals ; Antigens, Bacterial/metabolism ; CD4-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Female ; Fingolimod Hydrochloride/administration & dosage ; Humans ; Immunization ; Immunologic Memory ; Influenza A virus/physiology ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Lung/immunology ; Lung/virology ; Mice ; Mice, Inbred C57BL ; Orthomyxoviridae Infections/immunology ; Peptides/metabolism ; Vaccines, Synthetic
Chemical Substances	Antigens, Bacterial ; Influenza Vaccines ; Peptides ; Vaccines, Synthetic ; Fingolimod Hydrochloride (G926EC510T)
Language	English
Publishing date	2018-08-16
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/s41385-018-0065-9
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Article: Corrigendum: Impact of the Food Additive Titanium Dioxide (E171) on Gut Microbiota-Host Interaction.

Pinget, Gabriela / Tan, Jian / Janac, Bartlomiej / Kaakoush, Nadeem O / Angelatos, Alexandra Sophie / O'Sullivan, John / Koay, Yen Chin / Sierro, Frederic / Davis, Joel / Divakarla, Shiva Kamini / Khanal, Dipesh / Moore, Robert J / Stanley, Dragana / Chrzanowski, Wojciech / Macia, Laurence

Frontiers in nutrition

2019 Volume 6, Page(s) 100

Abstract: This corrects the article DOI: 10.3389/fnut.2019.00057.]. ...

Abstract	[This corrects the article DOI: 10.3389/fnut.2019.00057.].
Language	English
Publishing date	2019-07-02
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2019.00100
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Article: Impact of the Food Additive Titanium Dioxide (E171) on Gut Microbiota-Host Interaction.

Frontiers in nutrition

2019 Volume 6, Page(s) 57

Abstract: The interaction between gut microbiota and host plays a central role in health. Dysbiosis, detrimental changes in gut microbiota and inflammation have been reported in non-communicable diseases. While diet has a profound impact on gut microbiota ... ...

Abstract	The interaction between gut microbiota and host plays a central role in health. Dysbiosis, detrimental changes in gut microbiota and inflammation have been reported in non-communicable diseases. While diet has a profound impact on gut microbiota composition and function, the role of food additives such as titanium dioxide (TiO
Language	English
Publishing date	2019-05-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2019.00057
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Article ; Online: Y1 signalling has a critical role in allergic airway inflammation.

Macia, Laurence / Rao, Priya T / Wheway, Julie / Sierro, Frederic / Mackay, Fabienne / Herzog, Herbert

Immunology and cell biology

2011 Volume 89, Issue 8, Page(s) 882–888

Abstract: Asthma affects 300 million people worldwide, yet the mechanism behind this pathology has only been partially elucidated. The documented connection between psychological stress and airway inflammation strongly suggests the involvement of the nervous ... ...

Abstract	Asthma affects 300 million people worldwide, yet the mechanism behind this pathology has only been partially elucidated. The documented connection between psychological stress and airway inflammation strongly suggests the involvement of the nervous system and its secreted mediators, including neuropeptides, on allergic respiratory disease. In this study, we show that neuropeptide Y (NPY), a prominent neurotransmitter, which release is strongly upregulated during stress, exacerbates allergic airway inflammation (AAI) in mice, via its Y1 receptor. Our data indicate that the development of AAI was associated with elevated NPY expression in the lung and that lack of NPY-mediated signalling in NPYKO mice or its Y1 receptor in Y1KO mice significantly improved AAI. In vivo, eosinophilia in the bronchoalveolar fluid as well as circulating immunoglobulin E in response to AAI, were significantly reduced in NPY- and Y1-deficient compared with wild-type mice. These changes correlated with a blunting of the Th2 immune profile that is characteristic for AAI, as shown by the decreased release of interleukin-5 during ex vivo re-stimulation of T cells isolated from the thoracic draining lymph nodes of NPY- or Y1-deficient mice subjected to AAI. Taken together this study demonstrates that signalling through Y1-receptors emerges as a critical pathway for the development of airway inflammation and as such potentially opens novel avenues for therapeutic intervention in asthma.
MeSH term(s)	Animals ; Asthma/immunology ; Asthma/metabolism ; Bronchoalveolar Lavage Fluid/immunology ; Eosinophilia/immunology ; Immunoglobulin E/blood ; Interleukin-5/biosynthesis ; Lung/immunology ; Lung/pathology ; Mice ; Mice, Knockout ; Neuropeptide Y/metabolism ; Receptors, Neuropeptide Y/metabolism ; Respiratory Hypersensitivity/immunology ; Respiratory Hypersensitivity/metabolism ; Respiratory Hypersensitivity/pathology ; Respiratory System/immunology ; Respiratory System/metabolism ; Respiratory System/pathology ; Signal Transduction
Chemical Substances	Interleukin-5 ; Neuropeptide Y ; Receptors, Neuropeptide Y ; neuropeptide Y-Y1 receptor ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2011-03-08
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	10.1038/icb.2011.6
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