Health
Scientists identify the mechanism behind inflammasome activation by fungal pathogens
Scientists at St. Jude Children’s Research Hospital have identified the mechanism behind inflammasome activation caused by infection with fungal pathogens. Aspergillus fumigatus..Fungal infections, especially A. fumigatusIs the leading cause of infection-related deaths in people with a weakened immune system. This study provides clues to potential therapeutic approaches for treating infectious and inflammatory diseases.Survey results published online todayNature..
The inflammasome is an important sentry of the organism’s innate immune defense system. Our previous studies have shown that fungal pathogens activate the inflammasome, but the exact mechanism of action of inflammasome involvement remains unclear. “
Thirumala-Devi Kanneganti, Ph.D., Faculty of Immunology, St. Jude. , Corresponding author, founding member of the inflammasome field
To understand these mechanisms A. fumigatus, Scientists have sought pathogen-associated molecular patterns that can stimulate the innate immune response by activating the inflammasome. Scientists have focused on NLRP3, the most studied inflammasome sensor.
This study identified a new fungal pathogen-associated molecular pattern, galactosaminogalactan (GAG). GAG A. fumigatusInduced NLRP3 inflammasome activation.Scientists showed it A. fumigatus Insufficient GAG cannot induce inflammasome activation.Conversely, overproduction of GAG A. fumigatus Increases inflammasome activation.
In addition, inflammasome activation is important for clearing A. fumigatus Infectious diseases of animals.The· A. fumigatus Fungal strains that did not produce GAG were more toxic in mice, while strains that overproduced GAG were less toxic.
Similarly, activation of the inflammasome is protective during intestinal inflammation in a mouse model of colitis, an inflammatory disease. Treatment with purified GAG provided protection against colitis.
“We have shown that protection against this inflammatory disease depends on GAG’s ability to induce activation of the inflammasome,” said Dr. Benoit Briard, former lead author of St. Jude Immunology. .. “These findings point to a therapeutic mechanism for GAG in inflammatory diseases.”
Source:
Journal reference:
Briard, B. , et al. (2020) Galactosaminogalactan activates the inflammasome to protect the host. Nature. doi.org/10.1038/s41586-020-2996-z..
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