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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)
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author
organization
publishing date
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
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
2008-11-10 16:03:16
date last changed
2017-09-10 03:36:57
@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 &lt; 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},
  volume       = {173},
  year         = {2008},
}