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Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo

Rickettsiae can cause life-threatening infections in humans. Macrophages are one of the initial targets for rickettsiae after inoculation by ticks. However, it remains poorly understood how rickettsiae remain free in macrophages prior to establishing their infection in microvascular endothelial cell...

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Autores principales: Bechelli, Jeremy, Vergara, Leoncio, Smalley, Claire, Buzhdygan, Tetyana P., Bender, Sean, Zhang, William, Liu, Yan, Popov, Vsevolod L., Wang, Jin, Garg, Nisha, Hwang, Seungmin, Walker, David H., Fang, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300621/
https://www.ncbi.nlm.nih.gov/pubmed/30297526
http://dx.doi.org/10.1128/IAI.00651-18
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author Bechelli, Jeremy
Vergara, Leoncio
Smalley, Claire
Buzhdygan, Tetyana P.
Bender, Sean
Zhang, William
Liu, Yan
Popov, Vsevolod L.
Wang, Jin
Garg, Nisha
Hwang, Seungmin
Walker, David H.
Fang, Rong
author_facet Bechelli, Jeremy
Vergara, Leoncio
Smalley, Claire
Buzhdygan, Tetyana P.
Bender, Sean
Zhang, William
Liu, Yan
Popov, Vsevolod L.
Wang, Jin
Garg, Nisha
Hwang, Seungmin
Walker, David H.
Fang, Rong
author_sort Bechelli, Jeremy
collection PubMed
description Rickettsiae can cause life-threatening infections in humans. Macrophages are one of the initial targets for rickettsiae after inoculation by ticks. However, it remains poorly understood how rickettsiae remain free in macrophages prior to establishing their infection in microvascular endothelial cells. Here, we demonstrated that the concentration of Rickettsia australis was significantly greater in infected tissues of Atg5(flox/flox) mice than in the counterparts of Atg5(flox/flox) Lyz-Cre mice, in association with a reduced level of interleukin-1β (IL-1β) in serum. The greater concentration of R. australis in Atg5(flox/flox) bone marrow-derived macrophages (BMMs) than in Atg5(flox/flox) Lyz-Cre BMMs in vitro was abolished by exogenous treatment with recombinant IL-1β. Rickettsia australis induced significantly increased levels of light chain 3 (LC3) form II (LC3-II) and LC3 puncta in Atg5-competent BMMs but not in Atg5-deficient BMMs, while no p62 turnover was observed. Further analysis found the colocalization of LC3 with a small portion of R. australis and Rickettsia-containing double-membrane-bound vacuoles in the BMMs of B6 mice. Moreover, treatment with rapamycin significantly increased the concentrations of R. australis in B6 BMMs compared to those in the untreated B6 BMM controls. Taken together, our results demonstrate that Atg5 favors R. australis infection in mouse macrophages in association with a suppressed level of IL-1β production but not active autophagy flux. These data highlight the contribution of Atg5 in macrophages to the pathogenesis of rickettsial diseases.
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spelling pubmed-63006212018-12-28 Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo Bechelli, Jeremy Vergara, Leoncio Smalley, Claire Buzhdygan, Tetyana P. Bender, Sean Zhang, William Liu, Yan Popov, Vsevolod L. Wang, Jin Garg, Nisha Hwang, Seungmin Walker, David H. Fang, Rong Infect Immun Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Rickettsiae can cause life-threatening infections in humans. Macrophages are one of the initial targets for rickettsiae after inoculation by ticks. However, it remains poorly understood how rickettsiae remain free in macrophages prior to establishing their infection in microvascular endothelial cells. Here, we demonstrated that the concentration of Rickettsia australis was significantly greater in infected tissues of Atg5(flox/flox) mice than in the counterparts of Atg5(flox/flox) Lyz-Cre mice, in association with a reduced level of interleukin-1β (IL-1β) in serum. The greater concentration of R. australis in Atg5(flox/flox) bone marrow-derived macrophages (BMMs) than in Atg5(flox/flox) Lyz-Cre BMMs in vitro was abolished by exogenous treatment with recombinant IL-1β. Rickettsia australis induced significantly increased levels of light chain 3 (LC3) form II (LC3-II) and LC3 puncta in Atg5-competent BMMs but not in Atg5-deficient BMMs, while no p62 turnover was observed. Further analysis found the colocalization of LC3 with a small portion of R. australis and Rickettsia-containing double-membrane-bound vacuoles in the BMMs of B6 mice. Moreover, treatment with rapamycin significantly increased the concentrations of R. australis in B6 BMMs compared to those in the untreated B6 BMM controls. Taken together, our results demonstrate that Atg5 favors R. australis infection in mouse macrophages in association with a suppressed level of IL-1β production but not active autophagy flux. These data highlight the contribution of Atg5 in macrophages to the pathogenesis of rickettsial diseases. American Society for Microbiology 2018-12-19 /pmc/articles/PMC6300621/ /pubmed/30297526 http://dx.doi.org/10.1128/IAI.00651-18 Text en Copyright © 2018 Bechelli et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Bechelli, Jeremy
Vergara, Leoncio
Smalley, Claire
Buzhdygan, Tetyana P.
Bender, Sean
Zhang, William
Liu, Yan
Popov, Vsevolod L.
Wang, Jin
Garg, Nisha
Hwang, Seungmin
Walker, David H.
Fang, Rong
Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo
title Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo
title_full Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo
title_fullStr Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo
title_full_unstemmed Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo
title_short Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo
title_sort atg5 supports rickettsia australis infection in macrophages in vitro and in vivo
topic Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300621/
https://www.ncbi.nlm.nih.gov/pubmed/30297526
http://dx.doi.org/10.1128/IAI.00651-18
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