A team of scientists from Australia and Israel demonstrates that Candida Auris, a fungus associated with life-threatening and drug-resistant infections, escapes the host's innate immune response by destroying macrophages through metabolic reprogramming. The fungus is also capable of escaping antimicrobial inflammatory response.
The study findings revealed that Candida auris escapes immune recognition and containment by macrophages and causes macrophage destruction by inducing metabolic stress. By analyzing isolates of four different pathogenic clades of Candida auris, the scientists observed that macrophage escape and destruction by the fungus is a conserved mechanism.
Specifically, Candida auris was found to destroy macrophages by disrupting glycolytic metabolism. Simultaneously, the fungus showed the ability to escape recognition and elimination by the NLRP3 inflammasome. The NLRP3 inflammasome is a vital component of the innate immune system that mediates the activation of an inflammatory protease (caspase-1) and induces the secretion of pro-inflammatory cytokines in response to microbial infection.
Using Candida auris-infected mice, the scientists observed that the deletion of transcriptional activator TYE7 leads to the inhibition of its glycolytic metabolism, reduction of its ability to destroy macrophages, and inhibition of its ability to establish infection in the kidneys. These observations indicate that TYE7 serves as a vital transcriptional regulator of Candida auris metabolism and pathogenesis.
PS: One post-doctoral researcher in this study is Dr Harshini Weerasinghe of Monash University.
Also read the earlier post on Candida Auris by @Stimulus mind
https://elakiri.com/threads/🔴👨⚕️⚕️...ව-තුළ-ව්යාප්ථ-වීමේ-අවදානමක්-⚕️👨⚕️🔴.2097620/
The study findings revealed that Candida auris escapes immune recognition and containment by macrophages and causes macrophage destruction by inducing metabolic stress. By analyzing isolates of four different pathogenic clades of Candida auris, the scientists observed that macrophage escape and destruction by the fungus is a conserved mechanism.
Specifically, Candida auris was found to destroy macrophages by disrupting glycolytic metabolism. Simultaneously, the fungus showed the ability to escape recognition and elimination by the NLRP3 inflammasome. The NLRP3 inflammasome is a vital component of the innate immune system that mediates the activation of an inflammatory protease (caspase-1) and induces the secretion of pro-inflammatory cytokines in response to microbial infection.
Using Candida auris-infected mice, the scientists observed that the deletion of transcriptional activator TYE7 leads to the inhibition of its glycolytic metabolism, reduction of its ability to destroy macrophages, and inhibition of its ability to establish infection in the kidneys. These observations indicate that TYE7 serves as a vital transcriptional regulator of Candida auris metabolism and pathogenesis.
ABSTRACT
Candida auris causes life-threatening, drug-resistant infections. In addition to drug resistance, therapeutic innovation is hindered by our limited knowledge of the mechanisms used by C. auris to evade immunity and establish infection. Here we show that C. auris escapes phagocytic containment and kills macrophages, and demonstrate that the mechanisms rely on metabolic regulation. We found that C. auris-infected macrophages undergo immunometabolic reprogramming and increase glycolysis but this does not lead to the expected antimicrobial responses, as macrophages fail to activate IL-1β cytokine and curb C. auris growth. Further analysis showed that C. auris relies on its own metabolic capacity to egress from macrophages, cause macrophage metabolic stress and cell death, and establish infection in vivo. We identified a transcriptional regulator of C. auris metabolism and macrophage evasion, and further show that, contrary to several other pathogens, C. auris-induced macrophage metabolic dysfunction and death fail to activate the NLRP3 inflammasome. Consequently, inflammasome-dependent antimicrobial responses remain inhibited throughout infection. Our findings establish a pivotal role for metabolic regulation in enabling C. auris to eliminate macrophages while remaining immunologically silent to ensure its own survival.PS: One post-doctoral researcher in this study is Dr Harshini Weerasinghe of Monash University.
Also read the earlier post on Candida Auris by @Stimulus mind
https://elakiri.com/threads/🔴👨⚕️⚕️...ව-තුළ-ව්යාප්ථ-වීමේ-අවදානමක්-⚕️👨⚕️🔴.2097620/
