Dendritic cell are able to differentially recognize Sporothrix schenckii antigens and promote Th1/Th17 response in vitro.

Sporotrichosis is a disease caused by the dimorphic fungus Sporothrix schenckii. The main clinical manifestations occur in the skin, however the number of systemic and visceral cases has increased, especially in immunocompromised patients. Dendritic cells (DCs) are highly capable to recognize the fungus associated data and translate it into differential T cells responses both in vivo and in vitro. Although, the mechanisms involved in the interaction between DCs and S. schenckii are not fully elucidated. The present study investigated the phenotypic and functional changes in bone marrow dendritic cells (BMDCs) stimulated in vitro with the yeast form of S. schenckii or exoantigen (ExoAg) and its ability to trigger a cellular immune response in vitro. Our results demonstrated that the live yeast of S. schenckii and its exoantigen, at a higher dose, were able to activate BMDCs and made them capable of triggering T cell responses in vitro. Whereas the yeast group promoted more pronounced IFN-γ production rather than IL-17, the Exo100 group generated similar production of both cytokines. The exoantigen stimulus suggests a capability to deviate the immune response from an effector Th1 to an inflammatory Th17 response. Interestingly, only the Exo100 group promoted the production of IL-6 and a significant increase of TGF-β, in addition to IL-23 production. Interestingly, only Exo100 group was capable to promote the production of IL-6 and a significant increase on TGF-β, in addition with IL-23 detection. Our results demonstrated the plasticity of DCs in translating the data associated with the fungus S. schenckii and ExoAg into differential T cell responses in vitro. The possibility of using ex vivo-generated DCs as vaccinal and therapeutic tools for sporotrichosis is a challenge for the future.

Verdan FF ，Faleiros JC ，Ferreira LS ，Monnazzi LG ，Maia DC ，Tansine A ，Placeres MC ，Carlos IZ ，Santos-Junior RR ... -  《-》

Differential induction of Th1-prone immunity by human dendritic cells activated with Sporothrix schenckii of cutaneous and visceral origins to determine their different virulence.

Uenotsuchi T ，Takeuchi S ，Matsuda T ，Urabe K ，Koga T ，Uchi H ，Nakahara T ，Fukagawa S ，Kawasaki M ，Kajiwara H ，Yoshida S ，Moroi Y ，Furue M ... -  《INTERNATIONAL IMMUNOLOGY》

Mouse bone marrow-derived dendritic cells can phagocytize the Sporothrix schenckii, and mature and activate the immune response by secreting interleukin-12 and presenting antigens to T lymphocytes.

In sporotrichosis, dermal dendritic cells were considered to participate in induction of the immune responses against Sporothrix schenckii infection. However, it is still unclear whether and how dermal dendritic cells were involved in the progress. To clarify the pathogenic role of dermal dendritic cells (DC) in sporotrichosis, we examined the phagocytosis, maturation stages, cytokine production and antigen-presenting ability of mouse bone marrow-derived DC after stimulation with S. schenckii. By analysis of flow cytometry, electron microscope and confocal microscope, mouse bone marrow-derived DC were proved to be able to phagocytize the S. schenckii. The increased expression of CD40, CD80 and CD86 on the surface of S. schenckii-pulsed mouse bone marrow-derived DC was detected by flow cytometer, indicating that the S. schenckii-pulsed mouse bone marrow-derived DC underwent the maturation program. The secretory enhancement of interleukin (IL)-12, but not IL-4, was found in S. schenckii-pulsed mouse bone marrow-derived DC, suggesting the possible activation of T-helper 1 prone immune responses. Furthermore, S. schenckii-pulsed mouse bone marrow-derived DC were demonstrated to be capable of inducing the proliferation of T lymphocytes from BALB/c mice that were pre-sensitized with S. schenckii. Together, all the results implied that dermal DC may participate in the induction of immune responses against S. schenckii infection in sporotrichosis.

Kusuhara M ，Qian H ，Li X ，Tsuruta D ，Tsuchisaka A ，Ishii N ，Ohata C ，Furumura M ，Hashimoto T ... -  《-》

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

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.

Ferreira LS ，Gonçalves AC ，Portuondo DL ，Maia DC ，Placeres MC ，Batista-Duharte A ，Carlos IZ ... -  《-》

Immune Response Induced by an Immunodominant 60 kDa Glycoprotein of the Cell Wall of Sporothrix schenckii in Two Mice Strains with Experimental Sporotrichosis.

Alba-Fierro CA ，Pérez-Torres A ，Toriello C ，Pulido-Camarillo E ，López-Romero E ，Romo-Lozano Y ，Gutiérrez-Sánchez G ，Ruiz-Baca E ... -  《-》