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Ex Vivo Host Transcriptomics During Cryptococcus neoformans, Cryptococcus gattii, and Candida albicans Infection of Peripheral Blood Mononuclear Cells From South African Volunteers

Summary

Researchers studied how human immune cells respond to three different fungal infections that commonly affect people with weakened immune systems. By examining gene activity in blood cells exposed to these fungi, they discovered that each fungus triggers different immune responses, with Candida albicans causing a much stronger reaction than the two Cryptococcus species. Only one shared immune pathway was activated by all three fungi, suggesting each infection requires different immune mechanisms to fight off. These findings could help develop new treatments for serious fungal infections.

Background

Cryptococcus neoformans and Cryptococcus gattii cause cryptococcal meningitis, a leading fungal cause of HIV-related deaths globally with the majority occurring in Africa. Candida albicans is a well-studied opportunistic pathogen in immunocompromised hosts. The human immune response to cryptococcal infections remains understudied compared to Candida despite their severity.

Objective

To investigate the transcriptional response of peripheral blood mononuclear cells from healthy South African volunteers when exposed to C. neoformans, C. gattii, and C. albicans. The study aimed to identify unique gene expression signatures that differentiate these fungal pathogens and provide insights into host immune mechanisms.

Results

C. gattii induced 280 differentially expressed genes (DEGs) at 6 hours while C. neoformans had 30, with responses reversing at 24 hours. C. albicans induced substantially more DEGs (580 at 6 hours, 927 at 24 hours) with persistent inflammatory response. Only CXCL10 was shared as a proinflammatory pathway among all three pathogens, indicating distinct immune signatures.

Conclusion

The study identified unique transcriptional signatures differentiating C. neoformans and C. gattii from each other and from C. albicans in healthy controls. The findings provide a foundation for investigating gene expression signatures associated with cryptococcal meningitis severity and identifying novel therapeutic targets.
  • Published in:Journal of Infectious Diseases,
  • Study Type:Experimental Study,
  • Source: 10.1093/infdis/jiae410; PMID: 39158391
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