TLR5 or NLRC4 is necessary and sufficient for promotion of humoral immunity by flagellin

Matam Vijay-Kumar, Frederic A. Carvalho, Jesse D. Aitken, Nimita H. Fifadara, Andrew T. Gewirtz

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

The fact that some TLR-based vaccine adjuvants maintain function in TLR-deficient hosts highlights that their mechanism of function remains incompletely understood. Thus, we examined the ability of flagellin to induce cytokines and elicit/promote murine antibody responses upon deletion of the flagellin receptors TLR5 and/or NLRC4 (also referred to as IPAF) using a prime/boost regimen. In TLR5-KO mice, flagellin failed to induce NF-κB-regulated cytokines such as keratinocyte-derived chemokine (CXCL1) but induced WT levels of the inflammasome cytokine IL-18 (IL-1F4). Conversely, in NLRC4-KO mice, flagellin induced keratinocyte-derived chemokine, but not IL-18, whereas TLR5/NLRC4-DKO lacked induction of all cytokines measured. Flagellin/ovalbumin treatment resulted in high-antibody titers to both flagellin and ovalbumin in WT, TLR5-KO and DKO mice but did not elicit antibodies to either in TLR5/NLRC4-DKO mice. Thus, flagellin's ability to elicit/promote humoral immunity requires a germ-line-encoded receptor capable of recognizing this molecule. Such promotion of adaptive immunity can be effectively driven by either TLR5-mediated activation of NF-κB or NLRC4-mediated activation of the inflammasome.

Original languageEnglish (US)
Pages (from-to)3528-3534
Number of pages7
JournalEuropean Journal of Immunology
Volume40
Issue number12
DOIs
StatePublished - Dec 2010

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Vijay-Kumar, M., Carvalho, F. A., Aitken, J. D., Fifadara, N. H., & Gewirtz, A. T. (2010). TLR5 or NLRC4 is necessary and sufficient for promotion of humoral immunity by flagellin. European Journal of Immunology, 40(12), 3528-3534. https://doi.org/10.1002/eji.201040421