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Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication

Leptospira interrogans are pathogenic bacteria responsible for leptospirosis, a zoonosis impacting 1 million people per year worldwide. Leptospires can infect all vertebrates, but not all hosts develop similar symptoms. Human and cattle may suffer from mild to acute illnesses and are therefore consi...

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Autores principales: Santecchia, Ignacio, Bonhomme, Delphine, Papadopoulos, Stylianos, Escoll, Pedro, Giraud-Gatineau, Alexandre, Moya-Nilges, Maryse, Vernel-Pauillac, Frédérique, Boneca, Ivo Gomperts, Werts, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310662/
https://www.ncbi.nlm.nih.gov/pubmed/35899053
http://dx.doi.org/10.3389/fcimb.2022.936931
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author Santecchia, Ignacio
Bonhomme, Delphine
Papadopoulos, Stylianos
Escoll, Pedro
Giraud-Gatineau, Alexandre
Moya-Nilges, Maryse
Vernel-Pauillac, Frédérique
Boneca, Ivo Gomperts
Werts, Catherine
author_facet Santecchia, Ignacio
Bonhomme, Delphine
Papadopoulos, Stylianos
Escoll, Pedro
Giraud-Gatineau, Alexandre
Moya-Nilges, Maryse
Vernel-Pauillac, Frédérique
Boneca, Ivo Gomperts
Werts, Catherine
author_sort Santecchia, Ignacio
collection PubMed
description Leptospira interrogans are pathogenic bacteria responsible for leptospirosis, a zoonosis impacting 1 million people per year worldwide. Leptospires can infect all vertebrates, but not all hosts develop similar symptoms. Human and cattle may suffer from mild to acute illnesses and are therefore considered as sensitive to leptospirosis. In contrast, mice and rats remain asymptomatic upon infection, although they get chronically colonized in their kidneys. Upon infection, leptospires are stealth pathogens that partially escape the recognition by the host innate immune system. Although leptospires are mainly extracellular bacteria, it was suggested that they could also replicate within macrophages. However, contradictory data in the current literature led us to reevaluate these findings. Using a gentamicin–protection assay coupled to high-content (HC) microscopy, we observed that leptospires were internalized in vivo upon peritoneal infection of C57BL/6J mice. Additionally, three different serotypes of pathogenic L. interrogans and the saprophytic L. biflexa actively infected both human (PMA differentiated) THP1 and mouse RAW264.7 macrophage cell lines. Next, we assessed the intracellular fate of leptospires using bioluminescent strains, and we observed a drastic reduction in the leptospiral intracellular load between 3 h and 6 h post-infection, suggesting that leptospires do not replicate within these cells. Surprisingly, the classical macrophage microbicidal mechanisms (phagocytosis, autophagy, TLR–mediated ROS, and RNS production) were not responsible for the observed decrease. Finally, we demonstrated that the reduction in the intracellular load was associated with an increase of the bacteria in the supernatant, suggesting that leptospires exit both human and murine macrophages. Overall, our study reevaluated the intracellular fate of leptospires and favors an active entrance followed by a rapid exit, suggesting that leptospires do not have an intracellular lifestyle in macrophages.
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spelling pubmed-93106622022-07-26 Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication Santecchia, Ignacio Bonhomme, Delphine Papadopoulos, Stylianos Escoll, Pedro Giraud-Gatineau, Alexandre Moya-Nilges, Maryse Vernel-Pauillac, Frédérique Boneca, Ivo Gomperts Werts, Catherine Front Cell Infect Microbiol Cellular and Infection Microbiology Leptospira interrogans are pathogenic bacteria responsible for leptospirosis, a zoonosis impacting 1 million people per year worldwide. Leptospires can infect all vertebrates, but not all hosts develop similar symptoms. Human and cattle may suffer from mild to acute illnesses and are therefore considered as sensitive to leptospirosis. In contrast, mice and rats remain asymptomatic upon infection, although they get chronically colonized in their kidneys. Upon infection, leptospires are stealth pathogens that partially escape the recognition by the host innate immune system. Although leptospires are mainly extracellular bacteria, it was suggested that they could also replicate within macrophages. However, contradictory data in the current literature led us to reevaluate these findings. Using a gentamicin–protection assay coupled to high-content (HC) microscopy, we observed that leptospires were internalized in vivo upon peritoneal infection of C57BL/6J mice. Additionally, three different serotypes of pathogenic L. interrogans and the saprophytic L. biflexa actively infected both human (PMA differentiated) THP1 and mouse RAW264.7 macrophage cell lines. Next, we assessed the intracellular fate of leptospires using bioluminescent strains, and we observed a drastic reduction in the leptospiral intracellular load between 3 h and 6 h post-infection, suggesting that leptospires do not replicate within these cells. Surprisingly, the classical macrophage microbicidal mechanisms (phagocytosis, autophagy, TLR–mediated ROS, and RNS production) were not responsible for the observed decrease. Finally, we demonstrated that the reduction in the intracellular load was associated with an increase of the bacteria in the supernatant, suggesting that leptospires exit both human and murine macrophages. Overall, our study reevaluated the intracellular fate of leptospires and favors an active entrance followed by a rapid exit, suggesting that leptospires do not have an intracellular lifestyle in macrophages. Frontiers Media S.A. 2022-07-11 /pmc/articles/PMC9310662/ /pubmed/35899053 http://dx.doi.org/10.3389/fcimb.2022.936931 Text en Copyright © 2022 Santecchia, Bonhomme, Papadopoulos, Escoll, Giraud-Gatineau, Moya-Nilges, Vernel-Pauillac, Boneca and Werts https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Santecchia, Ignacio
Bonhomme, Delphine
Papadopoulos, Stylianos
Escoll, Pedro
Giraud-Gatineau, Alexandre
Moya-Nilges, Maryse
Vernel-Pauillac, Frédérique
Boneca, Ivo Gomperts
Werts, Catherine
Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication
title Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication
title_full Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication
title_fullStr Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication
title_full_unstemmed Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication
title_short Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication
title_sort alive pathogenic and saprophytic leptospires enter and exit human and mouse macrophages with no intracellular replication
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310662/
https://www.ncbi.nlm.nih.gov/pubmed/35899053
http://dx.doi.org/10.3389/fcimb.2022.936931
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