Study of the Sporothrix schenckii infection induced in wild type and knockout mice for the ASC component inflammasome

Abstract

The fungus Sporothrix schenckii is the responsible for the sporotrichosis, a cosmopolitan disease which mostly occurs in tropical and subtropical countries and affects mainly workers who have contact with soil and organic matter. The host immune system plays an effective role in the course of infection and the innate response recognizes fungal antigens (PAMPs-"Pathogen-associated molecular patterns") through pattern recognition receptors (PRR-"Pattern recognition receptor") present in macrophages. There are several types of PRRs including the NLR ("Nod-like receptors"), which are cytosolic receptors and together with the adapter molecule associated with apoptosis (ASC) and the enzyme caspase -1 it form a multiprotein complex known as inflammasome. By the receptor activation, ASC and caspase-1 will be respectively activated, causing the maturation of the cytokines pro-IL-1² and pro-IL-18. The link between the innate immune response and the adaptive response will be made through the release of cytokines by the interaction between macrophages and lymphocytes in antigen recognition. Therefore, ASC inflammasome component will be the focus of this study and by the determination the viability of macrophages and lymphocytes, determination of nitric oxide and quantification of IL- 1² and IFN-³ in the co-culture of these cell types to verify the immune response in C57BL/6 WT ("wild-type") and ASC-/- ("knockout") mice infected or not with the fungus S. schenckii. Studies undertaken to elucidate the immune response and the role of its components against the fungus infection are important for a better treatment and a better understanding of the microorganism itself. (AU)