miR‑4792 regulates inflammatory responses in Cryptococcus neoformans‑infected microglia

Int J Mol Med. 2021 Nov;48(5):198. doi: 10.3892/ijmm.2021.5031. Epub 2021 Sep 9.

Abstract

Investigating the factors that influence the inflammatory response of microglial cells is crucial for understanding the pathogenesis of cryptococcal meningitis (CM). MicroRNAs (miRNAs/miRs) play an important role in inducing host defenses and activating the immune response during microbial infection; however, the regulatory mechanisms of miRNAs in cryptococcal meningitis remain poorly defined. In a previous study, the authors assessed the miRNA profiles of THP‑1 (human acute monocytic leukemia cells) cells following Cryptococcus neoformans (C. neoformans) infection. In the present study, it was found that miR‑4792 expression was downregulated in BV2 cells infected with C. neoformans, whilst that of its target gene, epidermal growth factor receptor (EGFR), was upregulated. Infected cells in which miR‑4792 was overexpressed exhibited a decreased EGFR transcript expression, reduced mitogen‑activated protein kinase (MAPK) signaling and a decreased secretion of inflammatory cytokines. In addition, following antifungal treatment in patients with cryptococcal meningitis, the levels of miR‑4792 in the cerebrospinal fluid significantly increased, whilst the expression of EGFR significantly decreased. In addition, receiver operator characteristic analysis revealed miR‑4792 (AUCROC=0.75) and EGFR (AUCROC=0.79) as potential diagnostic markers in patients with cryptococcal meningitis.

Keywords: Cryptococcus neoformans; EGFR; MAPK; inflammatory cytokines; miR‑4792.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Base Sequence
  • Cell Line
  • Cryptococcosis / genetics*
  • Cryptococcosis / microbiology*
  • Cryptococcus neoformans / physiology*
  • Cytokines / biosynthesis
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Inflammation / genetics*
  • Inflammation / pathology
  • Male
  • Meningitis, Cryptococcal / immunology
  • Meningitis, Cryptococcal / microbiology
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microglia / metabolism*
  • Microglia / microbiology*
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism
  • THP-1 Cells
  • Young Adult

Substances

  • Cytokines
  • MIRN4792 microRNA, human
  • MicroRNAs
  • ErbB Receptors
  • Mitogen-Activated Protein Kinases