Differential role of the interleukin-17 axis and neutrophils in resolution of inhalational anthrax.
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.
Unité Interactions Hôte-Agents Pathogènes, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, La Tronche, France.
Kévin
K
Garraud
Aurélie
A
Cleret
Jacques
J
Mathieu
Daniel
D
Fiole
Yves
Y
Gauthier
Anne
A
Quesnel-Hellmann
Jean-Nicolas
JN
Tournier
D000818:Animals; D000881:Anthrax / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology / Q000472:pathogenicity*; D019570:Inhalation Exposure; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D053722:Receptors, Interleukin-17 / Q000172:deficiency; D016019:Survival Analysis
C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17