Shiga toxin-mediated disease in MyD88-deficient mice infected with Escherichia coli O157:H7.
Calderon Toledo, Carla LU ; Rogers, Trisha Jayne ; Svensson, Majlis LU ; Tati, Ramesh LU ; Fischer, Hans LU ; Svanborg, Catharina LU and Karpman, Diana LU
(2008)
In American Journal of Pathology
173(5).
p.1428-1439
- Abstract
- Toll-like receptors (TLRs) are key factors of innate immunity that detect pathogen invasion and trigger a host response. TLR4 can mediate a response through adaptor molecules, MyD88 or TRIF. In the present study, streptomycin-treated MyD88(-/-), Tlr4(-/-), Trif (Lps2/Lps2), and C57BL/6 wild-type (WT) mice were infected with either Shiga toxin (Stx)-producing or non-producing Escherichia coli O157:H7. Moderate to severe clinical signs of disease developed in MyD88(-/-) (n = 21/21), Tlr4(-/-) (n = 12/16), Trif (Lps2/Lps2) (n = 7/15) and WT mice (n = 6/20) infected with Stx-producing E. coli O157:H7 but not in mice inoculated with the Stx non-producing strain (n = 0/54, P < 0.001). MyD88(-/-) mice infected with Stx-producing E. coli... (More)
- Toll-like receptors (TLRs) are key factors of innate immunity that detect pathogen invasion and trigger a host response. TLR4 can mediate a response through adaptor molecules, MyD88 or TRIF. In the present study, streptomycin-treated MyD88(-/-), Tlr4(-/-), Trif (Lps2/Lps2), and C57BL/6 wild-type (WT) mice were infected with either Shiga toxin (Stx)-producing or non-producing Escherichia coli O157:H7. Moderate to severe clinical signs of disease developed in MyD88(-/-) (n = 21/21), Tlr4(-/-) (n = 12/16), Trif (Lps2/Lps2) (n = 7/15) and WT mice (n = 6/20) infected with Stx-producing E. coli O157:H7 but not in mice inoculated with the Stx non-producing strain (n = 0/54, P < 0.001). MyD88(-/-) mice infected with Stx-producing E. coli O157:H7 developed the most severe disease and had the highest bacterial burden. Hematological analysis of sick MyD88(-/-) mice showed reduced red blood cell counts and reticulocytosis, suggesting hemolysis. Thrombocytopenia developed in MyD88(-/-), Trif (Lps2/Lps2), and WT mice, and creatinine levels were elevated in both MyD88(-/-) and WT mice infected with the Stx-producing strain. Renal histopathology showed evidence of glomerular capillary congestion, tubular desquamation, and fibrinogen deposition, and intestinal histopathology showed mucosal injury, edema, and inflammation in sick mice. Administration of purified Stx2 to MyD88(-/-) and WT mice led to severe disease in both groups, suggesting that MyD88(-/-) mice are not more sensitive to Stx than WT mice. As MyD88(-/-) mice developed the most severe disease hematological and pathological changes, the results suggest that dysfunctional innate immune responses via MyD88 enhanced Stx-induced disease. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1262599
- author
- Calderon Toledo, Carla
LU
; Rogers, Trisha Jayne
; Svensson, Majlis
LU
; Tati, Ramesh
LU
; Fischer, Hans
LU
; Svanborg, Catharina
LU
and Karpman, Diana
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Pathology
- volume
- 173
- issue
- 5
- pages
- 1428 - 1439
- publisher
- American Society for Investigative Pathology
- external identifiers
-
- wos:000260726400018
- pmid:18832584
- scopus:55349142883
- pmid:18832584
- ISSN
- 1525-2191
- DOI
- 10.2353/ajpath.2008.071218
- language
- English
- LU publication?
- yes
- id
- 99c2ea82-8fdf-4e0e-be88-df2287980453 (old id 1262599)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18832584?dopt=Abstract
- date added to LUP
- 2016-04-01 11:53:15
- date last changed
- 2022-03-28 17:11:50
@article{99c2ea82-8fdf-4e0e-be88-df2287980453,
abstract = {{Toll-like receptors (TLRs) are key factors of innate immunity that detect pathogen invasion and trigger a host response. TLR4 can mediate a response through adaptor molecules, MyD88 or TRIF. In the present study, streptomycin-treated MyD88(-/-), Tlr4(-/-), Trif (Lps2/Lps2), and C57BL/6 wild-type (WT) mice were infected with either Shiga toxin (Stx)-producing or non-producing Escherichia coli O157:H7. Moderate to severe clinical signs of disease developed in MyD88(-/-) (n = 21/21), Tlr4(-/-) (n = 12/16), Trif (Lps2/Lps2) (n = 7/15) and WT mice (n = 6/20) infected with Stx-producing E. coli O157:H7 but not in mice inoculated with the Stx non-producing strain (n = 0/54, P < 0.001). MyD88(-/-) mice infected with Stx-producing E. coli O157:H7 developed the most severe disease and had the highest bacterial burden. Hematological analysis of sick MyD88(-/-) mice showed reduced red blood cell counts and reticulocytosis, suggesting hemolysis. Thrombocytopenia developed in MyD88(-/-), Trif (Lps2/Lps2), and WT mice, and creatinine levels were elevated in both MyD88(-/-) and WT mice infected with the Stx-producing strain. Renal histopathology showed evidence of glomerular capillary congestion, tubular desquamation, and fibrinogen deposition, and intestinal histopathology showed mucosal injury, edema, and inflammation in sick mice. Administration of purified Stx2 to MyD88(-/-) and WT mice led to severe disease in both groups, suggesting that MyD88(-/-) mice are not more sensitive to Stx than WT mice. As MyD88(-/-) mice developed the most severe disease hematological and pathological changes, the results suggest that dysfunctional innate immune responses via MyD88 enhanced Stx-induced disease.}},
author = {{Calderon Toledo, Carla and Rogers, Trisha Jayne and Svensson, Majlis and Tati, Ramesh and Fischer, Hans and Svanborg, Catharina and Karpman, Diana}},
issn = {{1525-2191}},
language = {{eng}},
number = {{5}},
pages = {{1428--1439}},
publisher = {{American Society for Investigative Pathology}},
series = {{American Journal of Pathology}},
title = {{Shiga toxin-mediated disease in MyD88-deficient mice infected with Escherichia coli O157:H7.}},
url = {{http://dx.doi.org/10.2353/ajpath.2008.071218}},
doi = {{10.2353/ajpath.2008.071218}},
volume = {{173}},
year = {{2008}},
}