Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 7 August 2018 / Approved: 8 August 2018 / Online: 8 August 2018 (04:32:10 CEST)

A peer-reviewed article of this Preprint also exists.

Quinello, C.; Souza Ferreira, L.; Picolli, I.; Loesch, M.L.; Portuondo, D.L.; Batista-Duharte, A.; Zeppone Carlos, I. Sporothrix schenckii Cell Wall Proteins-Stimulated BMDCs Are Able to Induce a Th1-Prone Cytokine Profile In Vitro. J. Fungi 2018, 4, 106. Quinello, C.; Souza Ferreira, L.; Picolli, I.; Loesch, M.L.; Portuondo, D.L.; Batista-Duharte, A.; Zeppone Carlos, I. Sporothrix schenckii Cell Wall Proteins-Stimulated BMDCs Are Able to Induce a Th1-Prone Cytokine Profile In Vitro. J. Fungi 2018, 4, 106.

Abstract

Sporotrichosis is a subcutaneous mycosis affecting humans and other animals that can be transmitted a zoonosis with cats as the main vector. The conventional anti-fungal 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 hours and analyzed for the surface expression of co-stimulatory molecules and TLR-4, as well as the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 hours 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 SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile, known to be protective against other fungal diseases. This result could lead to evaluate the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.

Keywords

Sporothrix schenckii; bone-marrow-derived dendritic cells; vaccine; sporotrichosis

Subject

Biology and Life Sciences, Immunology and Microbiology

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