Premium
Activation of TLR5 Protects Against Radiation, Acute Colitis, and Food‐Borne Pathogens
Author(s) -
VijayKumar Matam,
Aitken Jesse,
Neish Andrew,
Rojas Mauricio,
Gewirtz Andrew
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.320.7
Subject(s) - flagellin , tlr5 , medicine , population , colitis , lethal dose , immunology , microbiology and biotechnology , inflammation , pharmacology , tlr4 , biology , toxicology , receptor , tlr2 , environmental health
We investigated the safety and efficacy of systemically‐administered bacterial flagellin to protect mice against a variety of challenges. Compared to LPS, mice given flagellin experienced less weight loss, exhibited transient hypoglycemia and suffered no detectable lung inflammation. In addition, flagellin was a weak inducer of death in D‐galactosamine sensitized mice. Furthermore, flagellin was highly effective as a radioprotectant offering up to 100% protection against the mortality that uniformly occurred in PBS‐treated mice. Flagellin offered significant protection at doses from 1 to 100 ug and required both TLR5 and MyD88. Optimal protection resulted from administration 2 h prior to exposure to radiation but significant (about 60%) protection was observed when flagellin was administered 4 h post‐irradiation. A single 50 ug dose also conferred significant protection against acute DSS colitis, rotavirus infection, and Salmonella‐induced mortality. In conclusion, flagellin is less toxic in vivo than LPS and protects mice against a broad range of challenges and, as such, may have practical value in a scenario in which an at‐risk population requires rapidly administered non‐specific protection in anticipation of, or in response to, an array of disparate threats.