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Article: Le poumon est sensible aux effets locaux et à distance des microbiotes

Mathieu, Elliot / Marquant, Quentin / Descamps, Delphyne / Riffault, Sabine / Saint-Criq, Vinciane / Thomas, Muriel

Société francophone nutrition clinique et métabolisme (SFNCM) Nutrition clinique et métabolisme. 2021 Nov., v. 35, no. 4

2021

Abstract: The respiratory physiology is influenced by flows of microorganisms originating mainly from the bucconasal sphere but also by bacterial signals produced locally in the lung and remotely by the intestinal microbiota. This review describes the composition, ...

Abstract	The respiratory physiology is influenced by flows of microorganisms originating mainly from the bucconasal sphere but also by bacterial signals produced locally in the lung and remotely by the intestinal microbiota. This review describes the composition, establishment and functions of the lung microbiota as well as the relationships between the intestinal and pulmonary microbiota underlying the intestine–lung axis.
Keywords	intestinal microorganisms ; intestines ; lungs ; nutrition ; respiratory physiology
Language	English
Dates of publication	2021-11
Size	p. 242-252.
Publishing place	Elsevier Masson SAS
Document type	Article
ZDB-ID	1131758-9
ISSN	0985-0562
ISSN	0985-0562
DOI	10.1016/j.nupar.2021.04.002
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Screening antivirals with a mCherry-expressing recombinant bovine respiratory syncytial virus: a proof of concept using cyclopamine.

Fix, Jenna / Descamps, Delphyne / Galloux, Marie / Ferret, Cécile / Bouguyon, Edwige / Zohari, Siamak / Näslund, Katarina / Hägglund, Sara / Altmeyer, Ralf / Valarcher, Jean-François / Riffault, Sabine / Eléouët, Jean-François

Veterinary research

2023 Volume 54, Issue 1, Page(s) 36

Abstract: Bovine respiratory syncytial virus (BRSV) is a pathogenic pneumovirus and a major cause of acute respiratory infections in calves. Although different vaccines are available against BRSV, their efficiency remains limited, and no efficient and large-scale ... ...

Abstract	Bovine respiratory syncytial virus (BRSV) is a pathogenic pneumovirus and a major cause of acute respiratory infections in calves. Although different vaccines are available against BRSV, their efficiency remains limited, and no efficient and large-scale treatment exists. Here, we developed a new reverse genetics system for BRSV expressing the red fluorescent protein mCherry, based on a field strain isolated from a sick calf in Sweden. Although this recombinant fluorescent virus replicated slightly less efficiently compared to the wild type virus, both viruses were shown to be sensitive to the natural steroidal alkaloid cyclopamine, which was previously shown to inhibit human RSV replication. Our data thus point to the potential of this recombinant fluorescent BRSV as a powerful tool in preclinical drug discovery to enable high throughput compound screening.
MeSH term(s)	Animals ; Cattle ; Humans ; Respiratory Syncytial Virus, Bovine ; Respiratory Syncytial Virus Infections/drug therapy ; Respiratory Syncytial Virus Infections/veterinary ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Respiratory Syncytial Virus, Human/metabolism ; Cattle Diseases ; Antibodies, Viral
Chemical Substances	cyclopamine (ZH658AJ192) ; Antiviral Agents ; Antibodies, Viral
Language	English
Publishing date	2023-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	1146298-x
ISSN	1297-9716 ; 0928-4249
ISSN (online)	1297-9716
ISSN	0928-4249
DOI	10.1186/s13567-023-01165-x
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Article ; Online: Pulmonary Susceptibility of Neonates to Respiratory Syncytial Virus Infection: A Problem of Innate Immunity?

Drajac, Carole / Laubreton, Daphné / Riffault, Sabine / Descamps, Delphyne

Journal of immunology research

2017 Volume 2017, Page(s) 8734504

Abstract: Human respiratory syncytial virus (RSV) is a common and highly contagious viral agent responsible for acute lower respiratory infection in infants. This pathology characterized by mucus hypersecretion and a disturbed T cell immune response is one of the ... ...

Abstract	Human respiratory syncytial virus (RSV) is a common and highly contagious viral agent responsible for acute lower respiratory infection in infants. This pathology characterized by mucus hypersecretion and a disturbed T cell immune response is one of the major causes of infant hospitalization for severe bronchiolitis. Although different risk factors are associated with acute RSV bronchiolitis, the immunological factors contributing to the susceptibility of RSV infection in infants are not clearly elucidated. Epidemiological studies have established that the age at initial infection plays a central role in the severity of the disease. Thus, neonatal susceptibility is intrinsically linked to the immunological characteristics of the young pulmonary mucosa. Early life is a critical period for the lung development with the first expositions to external environmental stimuli and microbiota colonization. Furthermore, neonates display a lung immune system that profoundly differs to those from adults, with the predominance of type 2 immune cells. In this review, we discuss the latest information about the lung immune environment in the early period of life at a steady state and upon RSV infection and how we can modulate neonatal susceptibility to RSV infection.
MeSH term(s)	Cellular Microenvironment ; Disease Susceptibility ; Humans ; Immune Tolerance ; Immunity, Innate ; Immunomodulation ; Infant, Newborn ; Lung/immunology ; Lung/virology ; Respiratory Syncytial Virus Infections/immunology ; Respiratory Syncytial Virus, Human/physiology
Language	English
Publishing date	2017
Publishing country	Egypt
Document type	Journal Article ; Review
ZDB-ID	2817541-4
ISSN	2314-7156 ; 2314-8861
ISSN (online)	2314-7156
ISSN	2314-8861
DOI	10.1155/2017/8734504
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Article: Regulatory B Lymphocytes Colonize the Respiratory Tract of Neonatal Mice and Modulate Immune Responses of Alveolar Macrophages to RSV Infection in IL-10-Dependant Manner

Laubreton, Daphné / Drajac, Carole / Eléouët, Jean-François / Rameix-Welti, Marie-Anne / Lo-Man, Richard / Riffault, Sabine / Descamps, Delphyne

Viruses. 2020 July 29, v. 12, no. 8

2020

Abstract: Respiratory syncytial virus (RSV) is the prevalent pathogen of lower respiratory tract infections in children. The presence of neonatal regulatory B lymphocytes (nBreg) has been associated with a poor control of RSV infection in human newborns and with ... ...

Abstract	Respiratory syncytial virus (RSV) is the prevalent pathogen of lower respiratory tract infections in children. The presence of neonatal regulatory B lymphocytes (nBreg) has been associated with a poor control of RSV infection in human newborns and with bronchiolitis severity. So far, little is known about how nBreg may contribute to neonatal immunopathology to RSV. We tracked nBreg in neonatal BALB/c mice and we investigated their impact on lung innate immunity, especially their crosstalk with alveolar macrophages (AMs) upon RSV infection. We showed that the colonization by nBreg during the first week of life is a hallmark of neonatal lung whereas this population is almost absent in adult lung. This particular period of age when nBreg are abundant corresponds to the same period when RSV replication in lungs fails to generate a type-I interferons (IFN-I) response and is not contained. When neonatal AMs are exposed to RSV in vitro, they produce IFN-I that in turn enhances IL-10 production by nBreg. IL-10 reciprocally can decrease IFN-I secretion by AMs. Thus, our work identified nBreg as an important component of neonatal lungs and pointed out new immunoregulatory interactions with AMs in the context of RSV infection.
Keywords	B-lymphocytes ; Respiratory syncytial virus ; adults ; bronchiolitis ; children ; humans ; immune response ; immunomodulation ; immunopathology ; innate immunity ; interferons ; interleukin-10 ; lungs ; macrophages ; mice ; neonates ; pathogens ; secretion
Language	English
Dates of publication	2020-0729
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v12080822
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Article: The Role of Insulin Regulated Aminopeptidase in Endocytic Trafficking and Receptor Signaling in Immune Cells.

Descamps, Delphyne / Evnouchidou, Irini / Caillens, Vivien / Drajac, Carole / Riffault, Sabine / van Endert, Peter / Saveanu, Loredana

Frontiers in molecular biosciences

2020 Volume 7, Page(s) 583556

Abstract: Insulin regulated aminopeptidase (IRAP) is a type II transmembrane protein with broad tissue distribution initially identified as a major component of Glut4 storage vesicles (GSV) in adipocytes. Despite its almost ubiquitous expression, IRAP had been ... ...

Abstract	Insulin regulated aminopeptidase (IRAP) is a type II transmembrane protein with broad tissue distribution initially identified as a major component of Glut4 storage vesicles (GSV) in adipocytes. Despite its almost ubiquitous expression, IRAP had been extensively studied mainly in insulin responsive cells, such as adipocytes and muscle cells. In these cells, the enzyme displays a complex intracellular trafficking pattern regulated by insulin. Early studies using fusion proteins joining the IRAP cytosolic domain to various reporter proteins, such as GFP or the transferrin receptor (TfR), showed that the complex and regulated trafficking of the protein depends on its cytosolic domain. This domain contains several motifs involved in IRAP trafficking, as demonstrated by mutagenesis studies. Also, proteomic studies and yeast two-hybrid experiments showed that the IRAP cytosolic domain engages in multiple protein interactions with cytoskeleton components and vesicular trafficking adaptors. These findings led to the hypothesis that IRAP is not only a cargo of GSV but might be a part of the sorting machinery that controls GSV dynamics. Recent work in adipocytes, immune cells, and neurons confirmed this hypothesis and demonstrated that IRAP has a dual function. Its carboxy-terminal domain located inside endosomes is responsible for the aminopeptidase activity of the enzyme, while its amino-terminal domain located in the cytosol functions as an endosomal trafficking adaptor. In this review, we recapitulate the published protein interactions of IRAP and summarize the increasing body of evidence indicating that IRAP plays a role in intracellular trafficking of several proteins. We describe the impact of IRAP deletion or depletion on endocytic trafficking and the consequences on immune cell functions. These include the ability of dendritic cells to cross-present antigens and prime adaptive immune responses, as well as the control of innate and adaptive immune receptor signaling and modulation of inflammatory responses.
Language	English
Publishing date	2020-10-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2020.583556
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Article ; Online: Regulatory B Lymphocytes Colonize the Respiratory Tract of Neonatal Mice and Modulate Immune Responses of Alveolar Macrophages to RSV Infection in IL-10-Dependant Manner.

Laubreton, Daphné / Drajac, Carole / Eléouët, Jean-François / Rameix-Welti, Marie-Anne / Lo-Man, Richard / Riffault, Sabine / Descamps, Delphyne

Viruses

2020 Volume 12, Issue 8

Abstract	Respiratory syncytial virus (RSV) is the prevalent pathogen of lower respiratory tract infections in children. The presence of neonatal regulatory B lymphocytes (nBreg) has been associated with a poor control of RSV infection in human newborns and with bronchiolitis severity. So far, little is known about how nBreg may contribute to neonatal immunopathology to RSV. We tracked nBreg in neonatal BALB/c mice and we investigated their impact on lung innate immunity, especially their crosstalk with alveolar macrophages (AMs) upon RSV infection. We showed that the colonization by nBreg during the first week of life is a hallmark of neonatal lung whereas this population is almost absent in adult lung. This particular period of age when nBreg are abundant corresponds to the same period when RSV replication in lungs fails to generate a type-I interferons (IFN-I) response and is not contained. When neonatal AMs are exposed to RSV in vitro, they produce IFN-I that in turn enhances IL-10 production by nBreg. IL-10 reciprocally can decrease IFN-I secretion by AMs. Thus, our work identified nBreg as an important component of neonatal lungs and pointed out new immunoregulatory interactions with AMs in the context of RSV infection.
MeSH term(s)	Animals ; Animals, Newborn ; B-Lymphocyte Subsets/immunology ; B-Lymphocytes, Regulatory/immunology ; Cells, Cultured ; Immunity, Innate ; Interferon Type I/biosynthesis ; Interferon Type I/immunology ; Interleukin-10/immunology ; Interleukin-10/metabolism ; Lung/immunology ; Lung/virology ; Macrophages, Alveolar/immunology ; Mice ; Mice, Inbred BALB C ; Respiratory Syncytial Virus Infections/immunology ; Respiratory Syncytial Virus Infections/virology ; Respiratory Syncytial Viruses/immunology ; Respiratory Syncytial Viruses/physiology ; Spleen/immunology ; Turbinates/immunology ; Virus Replication
Chemical Substances	IL10 protein, mouse ; Interferon Type I ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2020-07-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12080822
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Article ; Online: Longitudinal study of the immune response and memory following natural bovine respiratory syncytial virus infections in cattle of different age.

Hägglund, Sara / Näslund, Katarina / Svensson, Anna / Lefverman, Cecilia / Enül, Hakan / Pascal, Leonore / Siltenius, Jari / Holzhauer, Menno / Delabouglise, Alexis / Österberg, Julia / Alvåsen, Karin / Olsson, Ulf / Eléouët, Jean-François / Riffault, Sabine / Taylor, Geraldine / Rodriguez, María Jose / Garcia Duran, Marga / Valarcher, Jean François

PloS one

2022 Volume 17, Issue 9, Page(s) e0274332

Abstract: Human and bovine respiratory syncytial virus (HRSV and BRSV) are closely genetically related and cause respiratory disease in their respective host. Whereas HRSV vaccines are still under development, a multitude of BRSV vaccines are used to reduce ... ...

Abstract	Human and bovine respiratory syncytial virus (HRSV and BRSV) are closely genetically related and cause respiratory disease in their respective host. Whereas HRSV vaccines are still under development, a multitude of BRSV vaccines are used to reduce clinical signs. To enable the design of vaccination protocols to entirely stop virus circulation, we aimed to investigate the duration, character and efficacy of the immune responses induced by natural infections. The systemic humoral immunity was monitored every two months during two years in 33 dairy cattle in different age cohorts following a natural BRSV outbreak, and again in selected individuals before and after a second outbreak, four years later. Local humoral and systemic cellular responses were also monitored, although less extensively. Based on clinical observations and economic losses linked to decreased milk production, the outbreaks were classified as moderate. Following the first outbreak, most but not all animals developed neutralising antibody responses, BRSV-specific IgG1, IgG2 and HRSV F- and HRSV N-reactive responses that lasted at least two years, and in some cases at least four years. In contrast, no systemic T cell responses were detected and only weak IgA responses were detected in some animals. Seronegative sentinels remained negative, inferring that no new infections occurred between the outbreaks. During the second outbreak, reinfections with clinical signs and virus shedding occurred, but the signs were milder, and the virus shedding was significantly lower than in naïve animals. Whereas the primary infection induced similar antibody titres against the prefusion and the post fusion form of the BRSV F protein, memory responses were significantly stronger against prefusion F. In conclusion, even if natural infections induce a long-lasting immunity, it would probably be necessary to boost memory responses between outbreaks, to stop the circulation of the virus and limit the potential role of previously infected adult cattle in the chain of BRSV transmission.
MeSH term(s)	Adult ; Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; Antibody Formation ; Cattle ; Cattle Diseases/epidemiology ; Child, Preschool ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Longitudinal Studies ; Respiratory Syncytial Virus Infections/epidemiology ; Respiratory Syncytial Virus, Bovine ; Respiratory Syncytial Virus, Human
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Immunoglobulin A ; Immunoglobulin G
Language	English
Publishing date	2022-09-16
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.0274332
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Article ; Online: Control of IFN-I responses by the aminopeptidase IRAP in neonatal C57BL/6 alveolar macrophages during RSV infection.

Drajac, Carole / Laubreton, Daphné / Marquant, Quentin / Chottin, Claire / Ferret, Cécile / Bouguyon, Edwige / Schwartz-Cornil, Isabelle / Saveanu, Loredana / Riffault, Sabine / Descamps, Delphyne

Mucosal immunology

2021 Volume 14, Issue 4, Page(s) 949–962

Abstract: Respiratory Syncytial Virus (RSV) is the major cause of lower respiratory tract infection in infants, in whom, the sensing of RSV by innate immune receptors and its regulation are still poorly described. However, the severe bronchiolitis following RSV ... ...

Abstract	Respiratory Syncytial Virus (RSV) is the major cause of lower respiratory tract infection in infants, in whom, the sensing of RSV by innate immune receptors and its regulation are still poorly described. However, the severe bronchiolitis following RSV infection in neonates has been associated with a defect in type I interferons (IFN-I) production, a cytokine produced mainly by alveolar macrophages (AMs) upon RSV infection in adults. In the present study, neonatal C57BL/6 AMs mobilized very weakly the IFN-I pathway upon RSV infection in vitro and failed to restrain virus replication. However, IFN-I productions by neonatal AMs were substantially increased by the deletion of Insulin-Responsive AminoPeptidase (IRAP), a protein previously involved in the regulation of IFN-I production by dendritic cells. Moreover, neonatal IRAP
MeSH term(s)	Animals ; Animals, Newborn ; Cystinyl Aminopeptidase/metabolism ; Disease Models, Animal ; Host-Pathogen Interactions/immunology ; Interferon Type I/metabolism ; Macrophages, Alveolar/immunology ; Macrophages, Alveolar/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Respiratory Syncytial Virus Infections/immunology ; Respiratory Syncytial Virus Infections/metabolism ; Respiratory Syncytial Virus Infections/virology ; Respiratory Syncytial Viruses ; Signal Transduction ; Toll-Like Receptors/metabolism ; Virus Replication
Chemical Substances	Interferon Type I ; Toll-Like Receptors ; Cystinyl Aminopeptidase (EC 3.4.11.3) ; leucyl-cystinyl aminopeptidase (EC 3.4.11.3)
Language	English
Publishing date	2021-04-12
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/s41385-021-00402-w
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Article ; Online: The microbiota plays a critical role in the reactivity of lung immune components to innate ligands.

Marquant, Quentin / Laubreton, Daphné / Drajac, Carole / Mathieu, Elliot / Bouguyon, Edwige / Noordine, Marie-Louise / Remot, Aude / Riffault, Sabine / Thomas, Muriel / Descamps, Delphyne

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2021 Volume 35, Issue 4, Page(s) e21348

Abstract: The gut microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the gut and/or lung microbiota in the education of pulmonary innate immune responses. Here, we tested whether the ... ...

Abstract	The gut microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the gut and/or lung microbiota in the education of pulmonary innate immune responses. Here, we tested whether the endogenous microbiota in general can modulate the reactivity of pulmonary tissue to pathogen stimuli by comparing the response of specific-pathogen-free (SPF) and germ-free (GF) mice. Thus, we observed earlier and greater inflammation in the pulmonary compartment of GF mice than that of SPF mice after intranasal instillation to lipopolysaccharide (LPS), a component of Gram-negative bacteria. Toll-like receptor 4 (TLR4) was more abundantly expressed in the lungs of GF mice than those of SPF mice at steady state, which could predispose the innate immunity of GF mice to strongly react to the environmental stimuli. Lung explants were stimulated with different TLR agonists or infected with the human airways pathogen, respiratory syncytial virus (RSV), resulting in greater inflammation under almost all conditions for the GF explants. Finally, alveolar macrophages (AM) from GF mice presented a higher innate immune response upon RSV infection than those of SPF mice. Overall, these data suggest that the presence of microbiota in SPF mice induced a process of innate immune tolerance in the lungs by a mechanism which remains to be elucidated. Our study represents a step forward to establishing the link between the microbiota and the immune reactivity of the lungs.
MeSH term(s)	Animals ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoalveolar Lavage Fluid/cytology ; Cytokines/genetics ; Cytokines/metabolism ; Gastrointestinal Microbiome/physiology ; Gene Expression Regulation/drug effects ; Germ-Free Life ; Inflammation/chemically induced ; Inflammation/metabolism ; Lipopolysaccharides/toxicity ; Lung/immunology ; Lung/metabolism ; Lung Diseases/chemically induced ; Male ; Mice ; Specific Pathogen-Free Organisms ; Tissue Culture Techniques ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism
Chemical Substances	Cytokines ; Lipopolysaccharides ; TLR4 protein, human ; Toll-Like Receptor 4
Language	English
Publishing date	2021-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202002338R
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Article: Paradigms of Lung Microbiota Functions in Health and Disease, Particularly, in Asthma.

Mathieu, Elliot / Escribano-Vazquez, Unai / Descamps, Delphyne / Cherbuy, Claire / Langella, Philippe / Riffault, Sabine / Remot, Aude / Thomas, Muriel

Frontiers in physiology

2018 Volume 9, Page(s) 1168

Abstract: Improvements in our knowledge of the gut microbiota have broadened our vision of the microbes associated with the intestine. These microbes are essential actors and protectors of digestive and extra-digestive health and, by extension, crucial for human ... ...

Abstract	Improvements in our knowledge of the gut microbiota have broadened our vision of the microbes associated with the intestine. These microbes are essential actors and protectors of digestive and extra-digestive health and, by extension, crucial for human physiology. Similar reconsiderations are currently underway concerning the endogenous microbes of the lungs, with a shift in focus away from their involvement in infections toward a role in physiology. The discovery of the lung microbiota was delayed by the long-held view that the lungs of healthy individuals were sterile and by sampling difficulties. The lung microbiota has a low density, and the maintenance of small numbers of bacteria seems to be a critical determinant of good health. This review aims to highlight how knowledge about the lung microbiota can change our conception of lung physiology and respiratory health. We provide support for this point of view with knowledge acquired about the gut microbiota and intestinal physiology. We describe the main characteristics of the lung microbiota and its functional impact on lung physiology, particularly in healthy individuals, after birth, but also in asthma. We describe some of the physiological features of the respiratory tract potentially favoring the installation of a dysbiotic microbiota. The gut microbiota feeds and matures the intestinal epithelium and is involved in immunity, when the principal role of the lung microbiota seems to be the orientation and balance of aspects of immune and epithelial responsiveness. This implies that the local and remote effects of bacterial communities are likely to be determinant in many respiratory diseases caused by viruses, allergens or genetic deficiency. Finally, we discuss the reciprocal connections between the gut and lungs that render these two compartments inseparable.
Language	English
Publishing date	2018-08-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2018.01168
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