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Human neutrophil response to Pseudomonas bacteriophages

Dwayne R. Roach, Sylvie Chollet-Martin, Benoît Noël, Vanessa Granger, Laurent Debarbieux, Luc de Chaisemartin
doi: https://doi.org/10.1101/786905
Dwayne R. Roach
1Department of Microbiology, Institut Pasteur, Paris 75015, France
2Department of Biology, San Diego State University, San Diego CA 92182, USA
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Sylvie Chollet-Martin
3Inflammation Chimiokines et Immunopathologie, INSERM, Fac. de Pharmacie, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry 92290, France
4APHP, UF Auto-immunité et Hypersensibilités, HUPNVS, Hôpital Bichat, Paris 75018, France
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Benoît Noël
3Inflammation Chimiokines et Immunopathologie, INSERM, Fac. de Pharmacie, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry 92290, France
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Vanessa Granger
3Inflammation Chimiokines et Immunopathologie, INSERM, Fac. de Pharmacie, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry 92290, France
4APHP, UF Auto-immunité et Hypersensibilités, HUPNVS, Hôpital Bichat, Paris 75018, France
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Laurent Debarbieux
1Department of Microbiology, Institut Pasteur, Paris 75015, France
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  • For correspondence: laurent.debarbieux@pasteur.fr luc.de-chaisemartin@aphp.fr
Luc de Chaisemartin
3Inflammation Chimiokines et Immunopathologie, INSERM, Fac. de Pharmacie, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry 92290, France
4APHP, UF Auto-immunité et Hypersensibilités, HUPNVS, Hôpital Bichat, Paris 75018, France
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  • For correspondence: laurent.debarbieux@pasteur.fr luc.de-chaisemartin@aphp.fr
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Abstract

The immune system offers several mechanisms of response to remove harmful microbes that invade the human body. As a first line of defense, neutrophils can remove pathogens by phagocytosis, inactivate them by the release of reactive oxygen species (ROS) or immobilize them by neutrophil extracellular traps (NETs). Although, recent studies have shown that bacteriophages (phages) make up a large portion of human microbiomes and are currently being explored as human antibacterial therapeutics, neutrophilic responses to phages are still elusive. Here, we show that exposure of isolated human resting neutrophils to high concentration of the Pseudomonas phage PAK_P1 led to a 2.8 fold increase in interleukin-8 (IL-8) secretion. Importantly, phage exposure did not further affect resting neutrophil apoptosis or induce necrosis, CD11 expression, oxidative burst, and NETs. Similarly, inflammatory stimuli activated neutrophil effector responses were unaffected by phage exposure. Our work suggest that phages are unlikely to inadvertently cause excessive neutrophil responses that could damage tissues and worsen disease. Because IL-8 functions as a chemoattractant directing immune cells to sites of infection and inflammation, phage-stimulated IL-8 production may boost host immune responses.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted September 30, 2019.
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Human neutrophil response to Pseudomonas bacteriophages
Dwayne R. Roach, Sylvie Chollet-Martin, Benoît Noël, Vanessa Granger, Laurent Debarbieux, Luc de Chaisemartin
bioRxiv 786905; doi: https://doi.org/10.1101/786905
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Human neutrophil response to Pseudomonas bacteriophages
Dwayne R. Roach, Sylvie Chollet-Martin, Benoît Noël, Vanessa Granger, Laurent Debarbieux, Luc de Chaisemartin
bioRxiv 786905; doi: https://doi.org/10.1101/786905

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