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Type: Journal article
Title: Shiga Toxin-Mediated Disease in MyD88-Deficient Mice Infected with Escherichia coli O157:H7
Author: Toledo, C.
Rogers, T.
Svensson, M.
Tati, R.
Fischer, H.
Svanborg, C.
Karpman, D.
Citation: American Journal of Pathology, 2008; 173(5):www1-www12
Publisher: Amer Soc Investigative Pathology Inc
Issue Date: 2008
ISSN: 0002-9440
Statement of
Carla Calderon Toledo, Trisha Jayne Rogers, Majlis Svensson, Ramesh Tati, Hans Fischer, Catharina Svanborg and Diana Karpman
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.
Description: © 2008 American Society for Investigative Pathology
RMID: 0020082841
DOI: 10.2353/ajpath.2008.071218
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Appears in Collections:Molecular and Biomedical Science publications

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