Differential role of the interleukin-17 axis and neutrophils in resolution of inhalational anthrax

Infect Immun. 2012 Jan;80(1):131-42. doi: 10.1128/IAI.05988-11. Epub 2011 Oct 24.

Abstract

The roles of interleukin-17 (IL-17) and neutrophils in the lung have been described as those of two intricate but independent players. Here we identify neutrophils as the primary IL-17-secreting subset of cells in a model of inhalation anthrax using A/J and C57BL/6 mice. With IL-17 receptor A knockout (IL-17RA-/-) mice, we confirmed that IL-17A/F signaling is instrumental in the self-recruitment of this population. We also show that the IL-17A/F axis is critical for surviving pulmonary infection, as IL-17RA-/- mice become susceptible to intranasal infection by Bacillus anthracis Sterne spores. Strikingly, infection with a fully virulent strain did not affect IL-17RA-/- mouse survival. Eventually, by depleting neutrophils in wild-type and IL-17RA-/- mice, we demonstrated the crucial role of IL-17-secreting neutrophils in mouse survival of infection by fully virulent B. anthracis. This work demonstrates the important roles of both IL-17 signaling and neutrophils in clearing this pathogen and surviving pulmonary B. anthracis infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthrax / immunology*
  • Bacillus anthracis / immunology
  • Bacillus anthracis / pathogenicity*
  • Inhalation Exposure*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / immunology*
  • Receptors, Interleukin-17 / deficiency
  • Survival Analysis

Substances

  • Il17ra protein, mouse
  • Interleukin-17
  • Receptors, Interleukin-17