Current Research on the Immune Response to Experimental Sporotrichosis

Abstract

Sporotrichosis is often manifested as a chronic granulomatous infection and the monocytes/macrophages play a central role in the host defense system. Surface components of Sporothrix schenckii have been characterized and suggestions have been made as to their possible role in pathogenicity. Ergosterol peroxide, cell-wall compounds (alkali-insoluble fraction-F1 and lipid extract-LEY), and exoantigen from the yeast form of the fungus have been characterized as virulence factors, activating both innate, by cytotoxins linked to the activation of reactive oxygen and nitrogen species (H2O2 and NO), and adaptive immune response to produce cytokines Th1 and Th2 profile. In this study, preliminary results have demonstrated that, in systemic sporotrichosis, TLR-4 triggers the innate immune response, activating an oxidative burst. These data represent the first report of the participation of TLR-4 in murine sporotrichosis, in the presence of lipids from the cell wall of S. schenckii. These results taken together may open new perspectives of study leading to an antifungal agent that could be used to benefit the entire population.

Sporothrix schenckii and Sporotrichosis

“…The ergosterol peroxide, found in a pathogenic fungus for the first time in S. schenckii, is formed as a protective mechanism to evade reactive oxygen species during phagocytosis and may also represent a virulence factor. Apparently, however, survival of virulent S. schenckii yeast cells after phagocytosis of polymorphonuclear host cells relies on other detoxification strategies besides the one leading to ergosterol peroxide synthesis (32,231).…”

Sporothrix brasiliensis produces the highest levels of oxidative stress in a murine model among the species of the Sporothrix schenckii complex

“…The ability of the fungal pathogen to cause disease depends on its survival in the host via evasion of the immune system, especially the antimicrobial mechanism of phagocytes 5,6 . Immune cell function is closely linked to the generation of reactive oxygen species (ROS) and is strongly influenced by the redox potential of the extracellular environment.…”

“…The pathogenic mechanisms of Sporothrix are quite complex, showing intra and interspecies variability depending on the host immune response 5,10 .…”

“…Cells of the host immune system, such as macrophages and neutrophils, can generate an oxidative burst following phagocytosis of fungal pathogens 5,12 .…”

Potential Use of I. suffruticosa in Treatment of Tuberculosis with Immune System Activation

“…TNF-α regulates production of chemokines by macrophages (Algood et al, 2006;Roach et al, 2002); chemokines can further induce transendothelial migration and coordinate recruitment of immune cells within the tissues. TNF-α activates macrophages in conjunction with the cytokine IFN-γ (Flesch & Kaufmann 1986;Roock et al, 1986;Carlos et al, 2009) such activated macrophages can kill intracellular mycobacteria. TNF-α can also induce necrotic or apoptotic cell death in macrophages (Laster et al, 1988) that is promoted by TB infection (Keane, et al, 2001).…”