Sporothrix schenckii Cell Wall Proteins-Stimulated BMDCs Are Able to Induce a Th1-Prone Cytokine Profile In Vitro

Abstract

Sporotrichosis is a subcutaneous mycosis affecting humans and other animals. The disease can be acquired by accidental inoculation of the fungus through the skin or through the respiratory system. Sporotrichosis can also be transmitted through bites or scratches by infected cats and more rarely by other animals (zoonotic transmission). Conventional antifungal therapy is especially inefficient in immunocompromised patients, who tend to develop the most severe forms of the disease, thus prompting the search for alternative therapies. Given their antigen-presenting properties, dendritic cells (DCs) have been used in both prophylactic and therapeutic vaccination strategies. Hence, this study aims to assess the use of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile induced by Sporothrix schenckii cell wall proteins (SsCWP)-stimulated, bone-marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 h and analyzed for the surface expression of costimulatory molecules and TLR-4, as well as for the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 h and had the same cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6, IL-17A, and TNF. On the other hand, higher levels of IFN-γ, IL-10, and IL-2 were found in the supernatants of the coculture as compared with the BMDCs alone; TNF secretion was almost completely abrogated, whereas IL-6 was only partially inhibited and IL-17A was unaffected. Our results thus suggest that SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile which is known to be protective against other fungal diseases. This result could lead to studies which evaluate the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.

Sporothrix schenckii regulates macrophage inflammatory responses via the c‐JUN‐induced Dab2 transcription

“…And, treatment with Amphotericin B (AmB) enhances the in vitro production of Il1β and Tnfα in peritoneal macrophages. 33 S. schenckii is able to promote BMDC maturation and increase Tnfα production, 34 and it seems that Tnfα contributes to the host defence against sporotrichosis infection. It has been reported that mast cells can be directly activated by inducing de novo synthesis of the inflammatory mediators, Tnfα and Il-6.…”

A Recombinant Enolase-Montanide™ PetGel A Vaccine Promotes a Protective Th1 Immune Response against a Highly Virulent Sporothrix schenckii by Toluene Exposure

“…Several studies revealed that Th1 response plays a decisive role in the defense against S. schenckii infection [32,33,34,35]. In this sense, activation of Th1 lymphocytes is becoming an interesting immunomodulatory strategy against sporotrichosis.…”

“…AFCo3 stimulated a strong Th1- and Th17 response associated with the antifungal effect of AmB, which significantly improved the fungal clearance [37]. Regarding vaccination, studies suggest that Th1 response is associated with anti-sporothrix vaccine protection [20,21,22,38,39] and the activation of dendritic cells by fungal wall proteins seems to be important in theTh1 bias [34]. However, the role of Th17 response to prevent sporotrichosis is controversial.…”

Special Issue “Sporothrix and Sporotrichosis”

“…The protein Gp70 has been one of the candidates to develop an anti- Sporothrix vaccine [17,18,19,20,21,22,23], but other alternatives, such as formulations using cell wall glycoproteins, have also provided promising results, which are underscored by the development of protective responses upon immunization with these preparations [24]. Here, Quinello et al, provide new information on the use of dendritic cells as alternatives to deliver fungal epitopes to stimulate a protective anti- Sporothrix response [25]. Mouse bone-marrow-derived dendritic cells were stimulated with S. schenckii cell wall proteins and then cocultured with splenocytes.…”

“…Mouse bone-marrow-derived dendritic cells were stimulated with S. schenckii cell wall proteins and then cocultured with splenocytes. As a result, the activated dendritic cells stimulated a cytokine profile suitable for the activation of the Th1 cell population, suggesting the cell wall preparation could lead to the establishment of a protective antifungal response [25]. Since the study was conducted in an in vitro setting, this observation still needs to be confirmed in the animal model of sporotrichosis.…”