Eosinophil-Associated Innate IL-17 Response Promotes Aspergillus fumigatus Lung Pathology

• Main Authors: Nathália Luísa Sousa de Oliveira Malacco, Milene Alvarenga Rachid, Isabella Luisa da Silva Gurgel, Tauany Rodrigues Moura, Pedro Henrique Ferreira Sucupira, Lirlândia Pires de Sousa, Daniele da Glória de Souza, Remo de Castro Russo, Mauro Martins Teixeira, Frederico Marianetti Soriani
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-01-01
• Series: Frontiers in Cellular and Infection Microbiology
• Subjects: Eosinophils role in inflammation; fungal infection; innate immunity; IL-17 innate response; eosinophil lung damage
• Online Access: https://www.frontiersin.org/article/10.3389/fcimb.2018.00453/full

Aspergillus fumigatus is a common widespread microorganism with environmental, biological and clinical relevance. After inhalation, swollen conidia can germinate, colonize and invade pulmonary tissues. Eosinophils have been described as key cells in A. fumigatus lung infection. However, their specific role in protecting or damaging lung tissue as well as their relatioship among different A. fumigatus strains is poorly understood. Previously, it has been reported that eosinophils are able to produce IL-17 and mediate an innate response that protected mice from infection using Af293 and CEA10 strains. Here, we have developed a set of new experiments with the CEA17-derived A1163 strain of A. fumigatus. Using ΔdblGATA1 mice, we demonstrate that eosinophils produce IL-17 and are involved in control of neutrophil, macrophage and lymphocyte recruitment. We found that eosinophils also induce high levels of cytokines and chemokines, generating an intense inflammatory process. Eosinophils are responsible for increased pulmonary dysfunction and elevated lethality rates in mice. Curiously, fungal burden was not affected. To address the role of IL-17 signaling, pharmacological inhibition of this mediator in the airways with anti-IL-17 antibody was able to reduce inflammation in the airways and protect infected mice. In conclusion, our results demonstrate that eosinophils control IL-17-mediated response and contribute to lung pathology after A. fumigatus infection. Therefore, eosinophils may represent a potential target for controlling exacerbated inflammation and prevent tissue damage during this fungal infection.