Optimal clearance of Sporothrix schenckii requires an intact Th17 response in a mouse model of systemic infection
| Autor: | Lucas Souza Ferreira, Deivys Leandro Portuondo, Alexander Batista-Duharte, Amanda Costa Gonçalves, Danielle Cardoso Geraldo Maia, Marisa Campos Polesi Placeres, Iracilda Zeppone Carlos |
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| Rok vydání: | 2014 |
| Předmět: |
Immunology
Biology Interleukin-23 Lymphocyte Depletion Microbiology Mice RAR-related orphan receptor gamma medicine Immunology and Allergy Sporothrix schenckii Animals Humans Antibodies Blocking Transcription factor Cells Cultured Orphan receptor Mice Inbred BALB C Sporotrichosis Multiple sclerosis Interleukins Sporothrix Interleukin-17 FOXP3 Hematology Nuclear Receptor Subfamily 1 Group F Member 3 Th1 Cells medicine.disease biology.organism_classification Disease Models Animal Rheumatoid arthritis Th17 Cells |
| Zdroj: | Immunobiology. 220(8) |
| ISSN: | 1878-3279 |
| Popis: | 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 γt (RORγt) 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. |
| Databáze: | OpenAIRE |
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