Flagellin treatment protects against chemicals, bacteria, viruses, and radiation

Matam Vijay Kumar, Jesse D. Aitken, Catherine J. Sanders, Amena Frias, Valerie M. Sloane, Jianguo Xu, Andrew S. Neish, Mauricio Rojas, Andrew T. Gewirtz

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Sudden exposure of human populations to chemicals, pathogens, or radiation has the potential to result in substantial morbidity. A potential means of rapidly protecting such populations might be to activate innate host defense pathways, which can provide broad protection against a variety of insults. However, innate immune activators can, by themselves, result in severe inflammatory pathology, which in large part is driven by hemopoietic-derived cytokines such as TNF-α. We reasoned that, because it preferentially activates epithelial cells, the TLR5 agonist flagellin might not induce severe inflammatory pathology and yet be an ideal agent to provide such non-specific protection, particularly at the mucosal surfaces that serve as a front line of host defense. In accordance, we observed that systemic treatment of mice with purified flagellin did not induce the serologic, histopathologic, and clinical hallmarks of inflammation that are induced by LPS but yet protected mice against chemicals, pathogens, and ionizing radiation. Flagellin-elicited radioprotection required TLR5, the TLR signaling adaptor MyD88, and was effective if given between 2 h before to 4 h after exposure to irradiation. Flagellin-elicited radioprotection was, in part, mediated via effects on cells in bone marrow but yet rescued mortality without a pronounced rescue of radiation-induced anemia or leukopenia. Thus, systemic administration of flagellin may be a relatively safe means of providing temporary non-specific protection against a variety of challenges.

Original languageEnglish (US)
Pages (from-to)8280-8285
Number of pages6
JournalJournal of Immunology
Volume180
Issue number12
DOIs
StatePublished - Jan 1 2008

Fingerprint

Flagellin
Radiation
Viruses
Bacteria
Pathology
Leukopenia
Ionizing Radiation
Bone Marrow Cells
Population
Anemia
Epithelial Cells
Cytokines
Inflammation
Morbidity
Mortality

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kumar, M. V., Aitken, J. D., Sanders, C. J., Frias, A., Sloane, V. M., Xu, J., ... Gewirtz, A. T. (2008). Flagellin treatment protects against chemicals, bacteria, viruses, and radiation. Journal of Immunology, 180(12), 8280-8285. https://doi.org/10.4049/jimmunol.180.12.8280
Kumar, Matam Vijay ; Aitken, Jesse D. ; Sanders, Catherine J. ; Frias, Amena ; Sloane, Valerie M. ; Xu, Jianguo ; Neish, Andrew S. ; Rojas, Mauricio ; Gewirtz, Andrew T. / Flagellin treatment protects against chemicals, bacteria, viruses, and radiation. In: Journal of Immunology. 2008 ; Vol. 180, No. 12. pp. 8280-8285.
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Kumar, MV, Aitken, JD, Sanders, CJ, Frias, A, Sloane, VM, Xu, J, Neish, AS, Rojas, M & Gewirtz, AT 2008, 'Flagellin treatment protects against chemicals, bacteria, viruses, and radiation', Journal of Immunology, vol. 180, no. 12, pp. 8280-8285. https://doi.org/10.4049/jimmunol.180.12.8280

Flagellin treatment protects against chemicals, bacteria, viruses, and radiation. / Kumar, Matam Vijay; Aitken, Jesse D.; Sanders, Catherine J.; Frias, Amena; Sloane, Valerie M.; Xu, Jianguo; Neish, Andrew S.; Rojas, Mauricio; Gewirtz, Andrew T.

In: Journal of Immunology, Vol. 180, No. 12, 01.01.2008, p. 8280-8285.

Research output: Contribution to journalArticle

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Kumar MV, Aitken JD, Sanders CJ, Frias A, Sloane VM, Xu J et al. Flagellin treatment protects against chemicals, bacteria, viruses, and radiation. Journal of Immunology. 2008 Jan 1;180(12):8280-8285. https://doi.org/10.4049/jimmunol.180.12.8280