Molecular Basis for the Activation of Human Innate Immune Response by the Flagellin Derived from Plant-Pathogenic Bacterium, Acidovorax avenae

Int J Mol Sci. 2021 Jun 28;22(13):6920. doi: 10.3390/ijms22136920.

Abstract

Acidovorax avenae is a flagellated, pathogenic bacterium to various plant crops that has also been found in human patients with haematological malignancy, fever, and sepsis; however, the exact mechanism for infection in humans is not known. We hypothesized that the human innate immune system could be responsive to the purified flagellin isolated from A. avenae, named FLA-AA. We observed the secretion of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-8 by treating FLA-AA to human dermal fibroblasts, as well as macrophages. This response was exclusively through TLR5, which was confirmed by using TLR5-overexpression cell line, 293/hTLR5, as well as TLR5-specific inhibitor, TH1020. We also observed the secretion of inflammatory cytokine, IL-1β, by the activation of NLRC4 with FLA-AA. Overall, our results provide a molecular basis for the inflammatory response caused by FLA-AA in cell-based assays.

Keywords: Acidovorax avenae; NLRC4; TLR5; flagellin.

MeSH terms

  • CARD Signaling Adaptor Proteins / metabolism
  • Calcium-Binding Proteins / metabolism
  • Comamonadaceae / chemistry*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Flagellin / pharmacology*
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / physiology*
  • Interleukin-18 / metabolism
  • Interleukin-6 / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CARD Signaling Adaptor Proteins
  • Calcium-Binding Proteins
  • Interleukin-18
  • Interleukin-6
  • NLRC4 protein, human
  • Tumor Necrosis Factor-alpha
  • Flagellin

Supplementary concepts

  • Acidovorax avenae