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Article ; Online: Neutrophils: from IBD to the gut microbiota.

Danne, Camille / Skerniskyte, Jurate / Marteyn, Benoit / Sokol, Harry

Nature reviews. Gastroenterology & hepatology

2023 Volume 21, Issue 3, Page(s) 184–197

Abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract that results from dysfunction in innate and/or adaptive immune responses. Impaired innate immunity, which leads to lack of control of an altered intestinal ...

Abstract	Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract that results from dysfunction in innate and/or adaptive immune responses. Impaired innate immunity, which leads to lack of control of an altered intestinal microbiota and to activation of the adaptive immune system, promotes a secondary inflammatory response that is responsible for tissue damage. Neutrophils are key players in innate immunity in IBD, but their roles have been neglected compared with those of other immune cells. The latest studies on neutrophils in IBD have revealed unexpected complexities, with heterogeneous populations and dual functions, both deleterious and protective, for the host. In parallel, interconnections between disease development, intestinal microbiota and neutrophils have been highlighted. Numerous IBD susceptibility genes (such as NOD2, NCF4, LRRK2, CARD9) are involved in neutrophil functions related to defence against microorganisms. Moreover, severe monogenic diseases involving dysfunctional neutrophils, including chronic granulomatous disease, are characterized by intestinal inflammation that mimics IBD and by alterations in the intestinal microbiota. This observation demonstrates the dialogue between neutrophils, gut inflammation and the microbiota. Neutrophils affect microbiota composition and function in several ways. In return, microbial factors, including metabolites, regulate neutrophil production and function directly and indirectly. It is crucial to further investigate the diverse roles played by neutrophils in host-microbiota interactions, both at steady state and in inflammatory conditions, to develop new IBD therapies. In this Review, we discuss the roles of neutrophils in IBD, in light of emerging evidence proving strong interconnections between neutrophils and the gut microbiota, especially in an inflammatory context.
MeSH term(s)	Humans ; Gastrointestinal Microbiome ; Neutrophils ; Microbiota ; Inflammatory Bowel Diseases ; Inflammation
Language	English
Publishing date	2023-12-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2493722-8
ISSN	1759-5053 ; 1759-5045
ISSN (online)	1759-5053
ISSN	1759-5045
DOI	10.1038/s41575-023-00871-3
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Article ; Online: The battle for oxygen during bacterial and fungal infections.

André, Antonin C / Laborde, Matthieu / Marteyn, Benoit S

Trends in microbiology

2022 Volume 30, Issue 7, Page(s) 643–653

Abstract: Bacterial and fungal pathogens face various microenvironmental conditions during infection. In addition to acidosis, nutrient consumption, and hypercapnia, pathogen infections are associated with hypoxia, which is induced by bacterial and fungal ... ...

Abstract	Bacterial and fungal pathogens face various microenvironmental conditions during infection. In addition to acidosis, nutrient consumption, and hypercapnia, pathogen infections are associated with hypoxia, which is induced by bacterial and fungal respiration during the formation of foci of infection or biofilms. Consequently, the in vivo interaction between host immune cells and pathogens is anticipated to occur mainly under low-oxygen conditions. Various infectious disease models have reported that pathogens benefit from hypoxia, which dampens the oxygen-dependent antimicrobial activities of macrophages and neutrophils, such as the production of reactive oxygen species (ROS). Due to their dual respiration capacity (aerobic and anaerobic) or phenotypical adaptation (e.g., dormancy), pathogens have the capacity to survive and disseminate in the absence of oxygen. In addition, hypoxia modulates various mechanisms of pathogen virulence, promoting the dissemination of pathogens. Further investigations are still required to evaluate the relative importance of oxygen on the capacity of pathogens to invade and colonize host organs and to better understand alternative strategies developed by immune cells to circumvent pathogen dissemination in the absence of oxygen. Addressing this important and fundamental question in various models of infection may direct the development of innovative therapeutic strategies.
MeSH term(s)	Humans ; Hypoxia ; Mycoses ; Neutrophils ; Oxygen ; Reactive Oxygen Species ; Virulence
Chemical Substances	Reactive Oxygen Species ; Oxygen (S88TT14065)
Language	English
Publishing date	2022-02-04
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2022.01.002
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Article: The battle for oxygen during bacterial and fungal infections

André, Antonin C. / Laborde, Matthieu / Marteyn, Benoit S.

Trends in microbiology. 2022,

2022

Abstract	Bacterial and fungal pathogens face various microenvironmental conditions during infection. In addition to acidosis, nutrient consumption, and hypercapnia, pathogen infections are associated with hypoxia, which is induced by bacterial and fungal respiration during the formation of foci of infection or biofilms. Consequently, the in vivo interaction between host immune cells and pathogens is anticipated to occur mainly under low-oxygen conditions. Various infectious disease models have reported that pathogens benefit from hypoxia, which dampens the oxygen-dependent antimicrobial activities of macrophages and neutrophils, such as the production of reactive oxygen species (ROS). Due to their dual respiration capacity (aerobic and anaerobic) or phenotypical adaptation (e.g., dormancy), pathogens have the capacity to survive and disseminate in the absence of oxygen. In addition, hypoxia modulates various mechanisms of pathogen virulence, promoting the dissemination of pathogens. Further investigations are still required to evaluate the relative importance of oxygen on the capacity of pathogens to invade and colonize host organs and to better understand alternative strategies developed by immune cells to circumvent pathogen dissemination in the absence of oxygen. Addressing this important and fundamental question in various models of infection may direct the development of innovative therapeutic strategies.
Keywords	acidosis ; biofilm ; dormancy ; fungi ; hypercapnia ; hypoxia ; infectious diseases ; macrophages ; neutrophils ; oxygen ; pathogens ; reactive oxygen species ; therapeutics ; virulence
Language	English
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2022.01.002
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Article ; Online: The selective advantage of facultative anaerobes relies on their unique ability to cope with changing oxygen levels during infection.

André, Antonin C / Debande, Lorine / Marteyn, Benoit S

Cellular microbiology

2021 Volume 23, Issue 8, Page(s) e13338

Abstract: Bacteria, including those that are pathogenic, have been generally classified according to their ability to survive and grow in the presence or absence of oxygen: aerobic and anaerobic bacteria, respectively. Strict aerobes require oxygen to grow (e.g., ... ...

Abstract	Bacteria, including those that are pathogenic, have been generally classified according to their ability to survive and grow in the presence or absence of oxygen: aerobic and anaerobic bacteria, respectively. Strict aerobes require oxygen to grow (e.g., Neisseria), and strict anaerobes grow exclusively without, and do not survive oxygen exposure (e.g., Clostridia); aerotolerant bacteria (e.g., Lactobacilli) are insensitive to oxygen exposure. Facultative anaerobes (e.g., E. coli) have the unique ability to grow in the presence or in the absence of oxygen and are thus well-adapted to these changing conditions, which may constitute an underestimated selective advantage for infection. In the WHO antibiotic-resistant 'priority pathogens' list, facultative anaerobes are overrepresented (8 among 12 listed pathogens), consistent with clinical studies performed in populations particularly susceptible to infectious diseases. Bacteria aerobic respiratory chain plays a central role in oxygen consumption, leading to the formation of hypoxic infectious sites (infectious hypoxia). Facultative anaerobes have developed a wide diversity of aerotolerance and anaerotolerance strategies in vivo. However, at a single cell level, the modulation of the intracellular oxygen level in host infected cells remains elusive and will be discussed in this review. In conclusion, the ability of facultative bacteria to evolve in the presence or the absence of oxygen is essential for their virulence strategy and constitute a selective advantage. TAKE AWAY: Most life-threatening pathogenic bacteria are facultative anaerobes. Only facultative anaerobes are aerotolerant, anaerotolerant and capable of consuming O
MeSH term(s)	Bacteria ; Bacteria, Anaerobic ; Escherichia coli ; Oxygen ; Oxygen Consumption
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2021-04-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1468320-9
ISSN	1462-5822 ; 1462-5814
ISSN (online)	1462-5822
ISSN	1462-5814
DOI	10.1111/cmi.13338
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Article ; Online: Reducing neutrophil exposure to oxygen allows their basal state maintenance.

Injarabian, Louise / Skerniskyte, Jurate / Giai Gianetto, Quentin / Witko-Sarsat, Véronique / Marteyn, Benoit S

Immunology and cell biology

2021 Volume 99, Issue 7, Page(s) 782–789

Abstract: Neutrophils are the most abundant circulating white blood cells and are the central players of the innate immune response. During their lifecycle, neutrophils mainly evolve under low oxygen conditions (0.1-4% ... ...

Abstract	Neutrophils are the most abundant circulating white blood cells and are the central players of the innate immune response. During their lifecycle, neutrophils mainly evolve under low oxygen conditions (0.1-4% O
MeSH term(s)	Extracellular Traps ; Leukocyte Count ; Neutrophil Activation ; Neutrophils ; Oxygen
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2021-06-05
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.12458
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Article ; Online: Neutrophil Metabolic Shift during their Lifecycle: Impact on their Survival and Activation.

Injarabian, Louise / Devin, Anne / Ransac, Stéphane / Marteyn, Benoit S

International journal of molecular sciences

2019 Volume 21, Issue 1

Abstract: Polymorphonuclear neutrophils (PMNs) are innate immune cells, which represent 50% to 70% of the total circulating leukocytes. How PMNs adapt to various microenvironments encountered during their life cycle, from the bone marrow, to the blood plasma ... ...

Abstract	Polymorphonuclear neutrophils (PMNs) are innate immune cells, which represent 50% to 70% of the total circulating leukocytes. How PMNs adapt to various microenvironments encountered during their life cycle, from the bone marrow, to the blood plasma fraction, and to inflamed or infected tissues remains largely unexplored. Metabolic shifts have been reported in other immune cells such as macrophages or lymphocytes, in response to local changes in their microenvironment, and in association with a modulation of their pro-inflammatory or anti-inflammatory functions. The potential contribution of metabolic shifts in the modulation of neutrophil activation or survival is anticipated even though it is not yet fully described. If neutrophils are considered to be mainly glycolytic, the relative importance of alternative metabolic pathways, such as the pentose phosphate pathway, glutaminolysis, or the mitochondrial oxidative metabolism, has not been fully considered during activation. This statement may be explained by the lack of knowledge regarding the local availability of key metabolites such as glucose, glutamine, and substrates, such as oxygen from the bone marrow to inflamed tissues. As highlighted in this review, the link between specific metabolic pathways and neutrophil activation has been outlined in many reports. However, the impact of neutrophil activation on metabolic shifts' induction has not yet been explored. Beyond its importance in neutrophil survival capacity in response to available metabolites, metabolic shifts may also contribute to neutrophil population heterogeneity reported in cancer (tumor-associated neutrophil) or auto-immune diseases (Low/High Density Neutrophils). This represents an active field of research. In conclusion, the characterization of neutrophil metabolic shifts is an emerging field that may provide important knowledge on neutrophil physiology and activation modulation. The related question of microenvironmental changes occurring during inflammation, to which neutrophils will respond to, will have to be addressed to fully appreciate the importance of neutrophil metabolic shifts in inflammatory diseases.
MeSH term(s)	Animals ; Cell Survival/immunology ; Humans ; Inflammation/immunology ; Inflammation/pathology ; Metabolic Networks and Pathways/immunology ; Mitochondria/immunology ; Mitochondria/pathology ; Neutrophil Activation ; Neutrophils/immunology ; Neutrophils/pathology ; Oxidation-Reduction
Language	English
Publishing date	2019-12-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21010287
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Article ; Online: Ascorbate maintains a low plasma oxygen level.

Injarabian, Louise / Scherlinger, Marc / Devin, Anne / Ransac, Stéphane / Lykkesfeldt, Jens / Marteyn, Benoit S

Scientific reports

2020 Volume 10, Issue 1, Page(s) 10659

Abstract: In human blood, oxygen is mainly transported by red blood cells. Accordingly, the dissolved oxygen level in plasma is expected to be limited, although it has not been quantified yet. Here, by developing dedicated methods and tools, we determined that ... ...

Abstract	In human blood, oxygen is mainly transported by red blood cells. Accordingly, the dissolved oxygen level in plasma is expected to be limited, although it has not been quantified yet. Here, by developing dedicated methods and tools, we determined that human plasma pO
MeSH term(s)	Animals ; Ascorbic Acid/blood ; Ascorbic Acid/metabolism ; Cell Line ; Cell Lineage/physiology ; Erythrocytes/metabolism ; Guinea Pigs ; HEK293 Cells ; Hep G2 Cells ; Humans ; Hypoxia/blood ; Hypoxia/metabolism ; Oxidation-Reduction ; Oxygen/blood ; Plasma/metabolism ; Solubility ; Ubiquinone/analogs & derivatives ; Ubiquinone/metabolism
Chemical Substances	Ubiquinone (1339-63-5) ; ubiquinol (M9NL0C577Y) ; Ascorbic Acid (PQ6CK8PD0R) ; Oxygen (S88TT14065)
Language	English
Publishing date	2020-06-30
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/s41598-020-67778-w
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Article ; Online: Escherichia coli killing by epidemiologically successful sublineages of Shigella sonnei is mediated by colicins.

De Silva, P Malaka / Bennett, Rebecca J / Kuhn, Lauriane / Ngondo, Patryk / Debande, Lorine / Njamkepo, Elisabeth / Ho, Brian / Weill, François-Xavier / Marteyn, Benoît S / Jenkins, Claire / Baker, Kate S

EBioMedicine

2023 Volume 97, Page(s) 104822

Abstract: Background: Shigella sp. are enteric pathogens which causes >125 million cases of shigellosis annually. S. sonnei accounts for about a quarter of those cases and is increasingly prevalent in industrialising nations. Being an enteric pathogen, S. sonnei ... ...

Abstract	Background: Shigella sp. are enteric pathogens which causes >125 million cases of shigellosis annually. S. sonnei accounts for about a quarter of those cases and is increasingly prevalent in industrialising nations. Being an enteric pathogen, S. sonnei benefits from outcompeting gut commensals such as Escherichia coli to establish itself and cause disease. There are numerous mechanisms that bacterial pathogens use to outcompete its rivals including molecules called colicins. A Type 6 Secretion System (T6SS) was recently described as contributing to E. coli killing in S. sonnei. Methods: We used Bulk Phenotyping of Epidemiological Replicates (BPER) which combined bacterial Genome Wide Association Studies (bGWAS) and high throughput phenotyping on a collection of S. sonnei surveillance isolates to identify the genetic features associated with E. coli killing and explore their relationship with epidemiological behaviour. We further explored the presence of colicins and T6SS components in the isolates using genomics, laboratory experimentation, and proteomics. Findings: Our bGWAS analysis returned known and novel colicin and colicin related genes as significantly associated with E. coli killing. In silico analyses identified key colicin clusters responsible for the killing phenotype associated with epidemiologically successful sub-lineages. The killing phenotype was not associated with the presence of a T6SS. Laboratory analyses confirmed the presence of the key colicin clusters and that killing was contact-independent. Interpretation: Colicins are responsible for E. coli killing by S. sonnei, not a T6SS. This phenotype contributes to shaping the observed epidemiology of S. sonnei and may contribute to its increasing prevalence globally. BPER is an epidemiologically relevant approach to phenotypic testing that enables the rapid identification of genetic drivers of phenotypic changes, and assessment of their relevance to epidemiology in natural settings. Funding: Biotechnology and Biological Sciences Research Council, Biotechnology and Biological Sciences Research Council Doctoral Training Partnership studentship, Wellcome Trust, Medical Research Council (UK), French National Research Agency.
MeSH term(s)	Humans ; Colicins/genetics ; Escherichia coli/genetics ; Shigella sonnei/genetics ; Genome-Wide Association Study ; Shigella
Chemical Substances	Colicins
Language	English
Publishing date	2023-10-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104822
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Article ; Online: Ascorbate deficiency increases progression of shigellosis in guinea pigs and mice infection models.

Skerniskyte, Jurate / Mulet, Céline / André, Antonin C / Anderson, Mark C / Injarabian, Louise / Buck, Achim / Prade, Verena M / Sansonetti, Philippe J / Reibel-Foisset, Sophie / Walch, Axel K / Lebel, Michel / Lykkesfeldt, Jens / Marteyn, Benoit S

Gut microbes

2023 Volume 15, Issue 2, Page(s) 2271597

Abstract: ... ...

Abstract	Shigella
MeSH term(s)	Guinea Pigs ; Humans ; Animals ; Rabbits ; Mice ; Dysentery, Bacillary/microbiology ; Gastrointestinal Microbiome ; Shigella ; Disease Models, Animal ; Shigella flexneri ; Ascorbic Acid ; Mammals
Chemical Substances	Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2023-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2575755-6
ISSN	1949-0984 ; 1949-0984
ISSN (online)	1949-0984
ISSN	1949-0984
DOI	10.1080/19490976.2023.2271597
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Article: The mub40 peptide for use in detecting neutrophil-mediated inflammation events

Anderson, Mark C / Injarabian, Louise / Andre, Antonin / Tournebize, Regis / Marteyn, Benoit S

Journal of visualized experiments. 2019 Jan. 07, , no. 143

2019

Abstract: Here, we provide a protocol involving the use of MUB40, a synthesized peptide with the ability to bind glycosylated lactoferrin stored at high concentrations in specific and tertiary granules of neutrophils. This protocol details how MUB40 conjugated ... ...

Abstract	Here, we provide a protocol involving the use of MUB40, a synthesized peptide with the ability to bind glycosylated lactoferrin stored at high concentrations in specific and tertiary granules of neutrophils. This protocol details how MUB40 conjugated directly to a fluorophore can be used to stain neutrophils in fixed/permeabilized tissues as well as how this can be used in live-cell imaging to assay for neutrophil activation and de-granulation. Neutrophil detection methods are limited to species-specific monoclonal antibodies, which are not always suitable for certain applications. MUB40 does not penetrate the cell membrane and is thus excluded from lactoferrin stored in non-activated/non-permeabilized neutrophils. MUB40 has the added benefit of recognizing lactoferrin from a broad host range, making it especially useful for comparing results in studies involving multiple research models, reducing the number of duplicate reagents, and simplifying protocols through single-step staining.
Keywords	cell membranes ; fluorescent dyes ; glycosylation ; host range ; image analysis ; inflammation ; lactoferrin ; models ; monoclonal antibodies ; neutrophils ; peptides ; staining ; tissues
Language	English
Dates of publication	2019-0107
Size	p. e58367.
Publishing place	Journal of Visualized Experiments
Document type	Article
ISSN	1940-087X
DOI	10.3791/58367
Database	NAL-Catalogue (AGRICOLA)

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