Th17 response and apoptosis in the evolution of Sporothrix schenckii-induced infection

Abstract

Sporotrichosis is commonly caused by traumatic inoculation of thermo-dimorphic fungus Sporothrix schenckii in the skin or subcutaneous tissues, as a zoonosis from animal scratches or injuries involving soil. Previous studies on a sporotrichosis animal model showed an increased host susceptibility period during infection's acute phase with depressed immune response. This susceptibility has been associated to the inflammatory process exacerbation and apoptosis induction on immune cells by the invading pathogen. Apoptosis has probably evolved as a host protection mechanism, exposing the intracellular pathogen to the immune system and preventing the pathogen to use the cell as a way to evade the response. Adding to that, there's evidence that the simultaneous recognition of PAMPs (pathogen-associated molecular patterns) and apoptotic cell debris generate a cytokine profile capable of promoting Th17 cells differentiation, whose primary function seems to be the elimination of pathogens not adequately handled by Th1 and Th2 cells. Recently we showed that dendritic cells exposed to S. schenckii antigens are able to promote a Th1/Th17 in vitro response. That said, we propose to evaluate the Th17 response and apoptosis involvement during S. schenckii infection, for these are important mechanisms, strategic to this disease understanding and to the establishment of an effective treatment. (AU)