Cargando…

Yersinia pestis Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague

The majority of human Yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. Once in the dermis, Y. pestis can evade the host’s innate immune response and subsequently disseminate to the draining lymph node (dLN). There, the pathogen replicates...

Descripción completa

Detalles Bibliográficos
Autores principales: Shannon, Jeffrey G., Hasenkrug, Aaron M., Dorward, David W., Nair, Vinod, Carmody, Aaron B., Hinnebusch, B. Joseph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760243/
https://www.ncbi.nlm.nih.gov/pubmed/23982068
http://dx.doi.org/10.1128/mBio.00170-13
_version_ 1782282744787632128
author Shannon, Jeffrey G.
Hasenkrug, Aaron M.
Dorward, David W.
Nair, Vinod
Carmody, Aaron B.
Hinnebusch, B. Joseph
author_facet Shannon, Jeffrey G.
Hasenkrug, Aaron M.
Dorward, David W.
Nair, Vinod
Carmody, Aaron B.
Hinnebusch, B. Joseph
author_sort Shannon, Jeffrey G.
collection PubMed
description The majority of human Yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. Once in the dermis, Y. pestis can evade the host’s innate immune response and subsequently disseminate to the draining lymph node (dLN). There, the pathogen replicates to large numbers, causing the pathognomonic bubo of bubonic plague. In this study, several cytometric and microscopic techniques were used to characterize the early host response to intradermal (i.d.) Y. pestis infection. Mice were infected i.d. with fully virulent or attenuated strains of dsRed-expressing Y. pestis, and tissues were analyzed by flow cytometry. By 4 h postinfection, there were large numbers of neutrophils in the infected dermis and the majority of cell-associated bacteria were associated with neutrophils. We observed a significant effect of the virulence plasmid (pCD1) on bacterial survival and neutrophil activation in the dermis. Intravital microscopy of i.d. Y. pestis infection revealed dynamic interactions between recruited neutrophils and bacteria. In contrast, very few bacteria interacted with dendritic cells (DCs), indicating that this cell type may not play a major role early in Y. pestis infection. Experiments using neutrophil depletion and a CCR7 knockout mouse suggest that dissemination of Y. pestis from the dermis to the dLN is not dependent on neutrophils or DCs. Taken together, the results of this study show a very rapid, robust neutrophil response to Y. pestis in the dermis and that the virulence plasmid pCD1 is important for the evasion of this response.
format Online
Article
Text
id pubmed-3760243
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher American Society of Microbiology
record_format MEDLINE/PubMed
spelling pubmed-37602432013-09-12 Yersinia pestis Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague Shannon, Jeffrey G. Hasenkrug, Aaron M. Dorward, David W. Nair, Vinod Carmody, Aaron B. Hinnebusch, B. Joseph mBio Research Article The majority of human Yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. Once in the dermis, Y. pestis can evade the host’s innate immune response and subsequently disseminate to the draining lymph node (dLN). There, the pathogen replicates to large numbers, causing the pathognomonic bubo of bubonic plague. In this study, several cytometric and microscopic techniques were used to characterize the early host response to intradermal (i.d.) Y. pestis infection. Mice were infected i.d. with fully virulent or attenuated strains of dsRed-expressing Y. pestis, and tissues were analyzed by flow cytometry. By 4 h postinfection, there were large numbers of neutrophils in the infected dermis and the majority of cell-associated bacteria were associated with neutrophils. We observed a significant effect of the virulence plasmid (pCD1) on bacterial survival and neutrophil activation in the dermis. Intravital microscopy of i.d. Y. pestis infection revealed dynamic interactions between recruited neutrophils and bacteria. In contrast, very few bacteria interacted with dendritic cells (DCs), indicating that this cell type may not play a major role early in Y. pestis infection. Experiments using neutrophil depletion and a CCR7 knockout mouse suggest that dissemination of Y. pestis from the dermis to the dLN is not dependent on neutrophils or DCs. Taken together, the results of this study show a very rapid, robust neutrophil response to Y. pestis in the dermis and that the virulence plasmid pCD1 is important for the evasion of this response. American Society of Microbiology 2013-08-27 /pmc/articles/PMC3760243/ /pubmed/23982068 http://dx.doi.org/10.1128/mBio.00170-13 Text en Copyright © 2013 Shannon et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Shannon, Jeffrey G.
Hasenkrug, Aaron M.
Dorward, David W.
Nair, Vinod
Carmody, Aaron B.
Hinnebusch, B. Joseph
Yersinia pestis Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague
title Yersinia pestis Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague
title_full Yersinia pestis Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague
title_fullStr Yersinia pestis Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague
title_full_unstemmed Yersinia pestis Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague
title_short Yersinia pestis Subverts the Dermal Neutrophil Response in a Mouse Model of Bubonic Plague
title_sort yersinia pestis subverts the dermal neutrophil response in a mouse model of bubonic plague
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760243/
https://www.ncbi.nlm.nih.gov/pubmed/23982068
http://dx.doi.org/10.1128/mBio.00170-13
work_keys_str_mv AT shannonjeffreyg yersiniapestissubvertsthedermalneutrophilresponseinamousemodelofbubonicplague
AT hasenkrugaaronm yersiniapestissubvertsthedermalneutrophilresponseinamousemodelofbubonicplague
AT dorwarddavidw yersiniapestissubvertsthedermalneutrophilresponseinamousemodelofbubonicplague
AT nairvinod yersiniapestissubvertsthedermalneutrophilresponseinamousemodelofbubonicplague
AT carmodyaaronb yersiniapestissubvertsthedermalneutrophilresponseinamousemodelofbubonicplague
AT hinnebuschbjoseph yersiniapestissubvertsthedermalneutrophilresponseinamousemodelofbubonicplague