Induction of adaptive immunity by flagellin does not require robust activation of innate immunity

Catherine J. Sanders, Luigi Franchi, Felix Yarovinsky, Satoshi Uematsu, Shizuo Akira, Gabriel Núñez, Andrew T. Gewirtz

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The ability of TLR agonists to promote adaptive immune responses is attributed to their ability to robustly activate innate immunity. However, it has been observed that, for adjuvants in actual use in research and vaccination, TLR signaling is dispensable for generating humoral immunity. Here, we examined the role of TLR5 and MyD88 in promoting innate and humoral immunity to flagellin using a prime/boost immunization regimen. We observed that eliminating TLR5 greatly reduced flagellin-induced cytokine production, except for IL-18, and ablated DC maturation but did not significantly impact flagellin's ability to promote humoral immunity. Elimination of MyD88, which will ablate signaling through TLR and IL-Iβ/IL-18 generated by Nod-like receptors, reduced, but did not eliminate flagellin's promotion of humoral immunity. in contrast, loss of the innate immune receptor for profilin-like protein (PLP), TLR11, greatly reduced the ability of PLP to elicit humoral immunity. Together, these results indicate that, firstly, the degree of innate immune activation induced by TLR agonists may be in great excess of that needed to promote humoral immunity and, secondly, there is considerable redundancy in mechanisms that promote the humoral immune response upon innate immune recognition of flagellin. Thus, it should be possible to design innate immune activators that are highly effective vaccine adjuvants yet avoid the adverse events associated with systemic TLR activation.

Original languageEnglish (US)
Pages (from-to)359-371
Number of pages13
JournalEuropean Journal of Immunology
Volume39
Issue number2
DOIs
StatePublished - Jun 25 2009

Keywords

  • Adjuvant
  • Cytokines
  • DC
  • Profilin-like protein
  • TLR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Induction of adaptive immunity by flagellin does not require robust activation of innate immunity'. Together they form a unique fingerprint.

  • Cite this

    Sanders, C. J., Franchi, L., Yarovinsky, F., Uematsu, S., Akira, S., Núñez, G., & Gewirtz, A. T. (2009). Induction of adaptive immunity by flagellin does not require robust activation of innate immunity. European Journal of Immunology, 39(2), 359-371. https://doi.org/10.1002/eji.200838804