Abstract
Abstract Background: The role of IL-17 and neutrophils in the lung has been described as two intricate but independent players, IL-17 triggering downstream recruitment of neutrophils. Methods: A/J, C57BL/6, IL-17RA-/-, CX3CR1+/gfp mice were infected intranasally by B. anthracis Sterne 7702, its toxin-defective derivative mutant RP42 and the fully virulent 17JB strains. Cytokine productions were evaluated in the broncho-alveolar lavage and the population identified by intra-cellular staining. Results: Here, we identify neutrophils as the primary IL-17-secreting cell subset in an inhalation model of anthrax infection. Using IL-17RA-/- mice, we confirm that IL-17A/F signaling is instrumental in the self-recruitment of this population. Moreover, we show that IL-17A/F axis is critical for survival to pulmonary infection as IL-17RA-/- mice become susceptible to intranasal infection by anthrax Sterne spores. Eventually, by depleting neutrophils in wild type and IL-17RA-/- mice, we demonstrate the crucial role of IL-17-secreting neutrophils for mouse survival after anthrax infection in the Sterne strain model. In accordance, following intranasal infection with a fully virulent strain, neutrophils prove to be critical for survival. Conclusion: This work demonstrates the very intricate role of both IL-17 and neutrophils in the clearance of pathogen and survival to pulmonary anthrax.
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