Optimal clearance of Sporothrix schenckii requires an intact Th17 response in a mouse model of systemic infection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Processo FAPESP: 2012/24187-0

The discovery of Th17 cells, along with many other Th cell subsets in the recent years, has expanded the Th1/Th2 paradigm that had persisted since its proposition by Mosmann in 1986. Defined by the characteristic expression of the transcription factor retinoic-related orphan receptor gamma t (ROR gamma t) and production of IL-17A (IL-17), Th17 cells are powerful inducers of tissue inflammation with a recognized role against extracellular bacteria and fungi. Despite this, the interest in their study came from the pivotal role they play in the development and maintenance of major chronic inflammatory conditions such as multiple sclerosis, rheumatoid arthritis and Crohn's disease, hence they have been the target of promising new anti-Th17 therapies. Accordingly, the identification of opportunistic pathogens whose clearance relies on the Th17 response is of huge prophylactic importance. As shown here for the first time, this applies to Sporothrix schenckii, a thermo-dimorphic fungus and the causative agent of sporotrichosis. Our results show that both Th17 and Th1/Th17 mixed cells are developed during the S. schenckii systemic mice infection, which also leads to augmented production of IL-17 and IL-22. Also, by using an antibody-mediated IL-23 depletion model, we further demonstrate that optimal fungal clearance, but not survival, depends on an intact Th17 response. (C) 2015 Elsevier GmbH. All rights reserved.