Lipopolysaccharide renders transgenic mice expressing human serum amyloid P component sensitive to Shiga toxin 2.
Transgenic C57BL/6 mice expressing human serum amyloid P component (HuSAP) are resistant to Shiga toxin 2 (Stx2) at dosages that are lethal in HuSAP-negative wild-type mice. However, it is well established that Stx2 initiates extra-intestinal complications such as the haemolytic-uremic syndrome desp...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2011-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3123346?pdf=render |
id |
doaj-574a14306d43403eac36037931ff57d4 |
---|---|
record_format |
Article |
spelling |
doaj-574a14306d43403eac36037931ff57d42020-11-25T02:00:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2145710.1371/journal.pone.0021457Lipopolysaccharide renders transgenic mice expressing human serum amyloid P component sensitive to Shiga toxin 2.Thomas P GrienerJonathan G StreckerRomney M HumphriesGeorge L MulveyCarmen FuentealbaRobert E W HancockGlen D ArmstrongTransgenic C57BL/6 mice expressing human serum amyloid P component (HuSAP) are resistant to Shiga toxin 2 (Stx2) at dosages that are lethal in HuSAP-negative wild-type mice. However, it is well established that Stx2 initiates extra-intestinal complications such as the haemolytic-uremic syndrome despite the presence of HuSAP in human sera. We now demonstrate that co-administering purified Escherichia coli O55 lipopolysaccharide (LPS), at a dosage of 300 ng/g body weight, to HuSAP-transgenic mice increases their susceptibility to the lethal effects of Stx2. The enhanced susceptibility to Stx2 correlated with an increased expression of genes encoding the pro-inflammatory cytokine TNFα and chemokines of the CXC and CC families in the kidneys of LPS-treated mice, 48 hours after the Stx2/LPS challenge. Co-administering the glucocorticoid dexamethasone, but not the LPS neutralizing cationic peptide LL-37, protected LPS-sensitized HuSAP-transgenic mice from lethal doses of Stx2. Dexamethasone protection was specifically associated with decreased expression of the same inflammatory mediators (CXC and CC-type chemokines and TNFα) linked to enhanced susceptibility caused by LPS. The studies reveal further details about the complex cascade of host-related events that are initiated by Stx2 as well as establish a new animal model system in which to investigate strategies for diminishing serious Stx2-mediated complications in humans infected with enterohemorrhagic E. coli strains.http://europepmc.org/articles/PMC3123346?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Thomas P Griener Jonathan G Strecker Romney M Humphries George L Mulvey Carmen Fuentealba Robert E W Hancock Glen D Armstrong |
spellingShingle |
Thomas P Griener Jonathan G Strecker Romney M Humphries George L Mulvey Carmen Fuentealba Robert E W Hancock Glen D Armstrong Lipopolysaccharide renders transgenic mice expressing human serum amyloid P component sensitive to Shiga toxin 2. PLoS ONE |
author_facet |
Thomas P Griener Jonathan G Strecker Romney M Humphries George L Mulvey Carmen Fuentealba Robert E W Hancock Glen D Armstrong |
author_sort |
Thomas P Griener |
title |
Lipopolysaccharide renders transgenic mice expressing human serum amyloid P component sensitive to Shiga toxin 2. |
title_short |
Lipopolysaccharide renders transgenic mice expressing human serum amyloid P component sensitive to Shiga toxin 2. |
title_full |
Lipopolysaccharide renders transgenic mice expressing human serum amyloid P component sensitive to Shiga toxin 2. |
title_fullStr |
Lipopolysaccharide renders transgenic mice expressing human serum amyloid P component sensitive to Shiga toxin 2. |
title_full_unstemmed |
Lipopolysaccharide renders transgenic mice expressing human serum amyloid P component sensitive to Shiga toxin 2. |
title_sort |
lipopolysaccharide renders transgenic mice expressing human serum amyloid p component sensitive to shiga toxin 2. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
Transgenic C57BL/6 mice expressing human serum amyloid P component (HuSAP) are resistant to Shiga toxin 2 (Stx2) at dosages that are lethal in HuSAP-negative wild-type mice. However, it is well established that Stx2 initiates extra-intestinal complications such as the haemolytic-uremic syndrome despite the presence of HuSAP in human sera. We now demonstrate that co-administering purified Escherichia coli O55 lipopolysaccharide (LPS), at a dosage of 300 ng/g body weight, to HuSAP-transgenic mice increases their susceptibility to the lethal effects of Stx2. The enhanced susceptibility to Stx2 correlated with an increased expression of genes encoding the pro-inflammatory cytokine TNFα and chemokines of the CXC and CC families in the kidneys of LPS-treated mice, 48 hours after the Stx2/LPS challenge. Co-administering the glucocorticoid dexamethasone, but not the LPS neutralizing cationic peptide LL-37, protected LPS-sensitized HuSAP-transgenic mice from lethal doses of Stx2. Dexamethasone protection was specifically associated with decreased expression of the same inflammatory mediators (CXC and CC-type chemokines and TNFα) linked to enhanced susceptibility caused by LPS. The studies reveal further details about the complex cascade of host-related events that are initiated by Stx2 as well as establish a new animal model system in which to investigate strategies for diminishing serious Stx2-mediated complications in humans infected with enterohemorrhagic E. coli strains. |
url |
http://europepmc.org/articles/PMC3123346?pdf=render |
work_keys_str_mv |
AT thomaspgriener lipopolysacchariderenderstransgenicmiceexpressinghumanserumamyloidpcomponentsensitivetoshigatoxin2 AT jonathangstrecker lipopolysacchariderenderstransgenicmiceexpressinghumanserumamyloidpcomponentsensitivetoshigatoxin2 AT romneymhumphries lipopolysacchariderenderstransgenicmiceexpressinghumanserumamyloidpcomponentsensitivetoshigatoxin2 AT georgelmulvey lipopolysacchariderenderstransgenicmiceexpressinghumanserumamyloidpcomponentsensitivetoshigatoxin2 AT carmenfuentealba lipopolysacchariderenderstransgenicmiceexpressinghumanserumamyloidpcomponentsensitivetoshigatoxin2 AT robertewhancock lipopolysacchariderenderstransgenicmiceexpressinghumanserumamyloidpcomponentsensitivetoshigatoxin2 AT glendarmstrong lipopolysacchariderenderstransgenicmiceexpressinghumanserumamyloidpcomponentsensitivetoshigatoxin2 |
_version_ |
1724961623527915520 |