Transcriptomic analysis reveals that mTOR pathway can be modulated in macrophage cells by the presence of

Alícia C Piffer1, Francine M Dos Santos1, Marcos P Thomé1

  • 1Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Porto Alegre, RS, Brazil.

Insights

Cryptococcus fungi manipulate macrophage activity by altering gene expression, specifically downregulating the mTOR pathway. This fungal manipulation may enhance pathogen survival during cryptococcosis infection.

Area of Science:

  • Mycology
  • Immunology
  • Molecular Biology

Background:

  • Cryptococcus neoformans and Cryptococcus gattii cause cryptococcosis, a severe infectious disease.
  • Fungal pathogens reside and replicate within macrophages, crucial immune cells.
  • Understanding host-pathogen interactions is key to combating cryptococcosis.

Purpose of the Study:

  • To investigate the molecular mechanisms by which Cryptococcus spp. modulate macrophage activity.
  • To perform a genome-scale analysis of transcriptional changes in macrophages upon Cryptococcus exposure.

Main Methods:

  • Comparative genomic analysis of transcriptional changes in macrophages.
  • Exposure of macrophages to Cryptococcus spp. fungal cells.
  • Gene expression profiling and protein phosphorylation analysis.

Main Results:

  • Nearly 40 genes showed altered expression in macrophages exposed to Cryptococcus.
  • Genes associated with the mTOR pathway exhibited decreased expression.
  • Decreased phosphorylation of p70S6K and GSK-3β was observed in infected macrophages.

Conclusions:

  • Cryptococcus modulates the host macrophage mTOR pathway.
  • This modulation potentially enhances fungal survival within macrophages.
  • Targeting the mTOR pathway could be a therapeutic strategy against cryptococcosis.