The Role of SREC-Ⅰ in Innate Immunity to Aspergillus fumigatus Keratitis

Invest Ophthalmol Vis Sci. 2021 Jul 1;62(9):12. doi: 10.1167/iovs.62.9.12.

Abstract

Purpose: To determine the role of scavenger receptor expressed by endothelial cell-1 (SREC-Ⅰ) in vitro and in a mouse model of Aspergillus fumigatus keratitis.

Methods: SREC-Ⅰ mRNA and protein expression were tested in both normal and A fumigatus stimulated human corneal epithelial cells (HCECs). Immunofluorescence was used to detect SREC-Ⅰ expression in human corneas with or without A fumigatus infection. HCECs were incubated with SREC-Ⅰ small interfering RNA, then the mRNA levels of LOX-1, IL-1β, and TNF-α were detected after A fumigatus stimulation. A mouse fungal keratitis (FK) model was established and SREC-Ⅰ mRNA and protein expression were detected by RT-PCR, Western blot and immunofluorescence. The severity of FK was evaluated by clinical score. CLCX1, LOX-1, IL-1β, and TNF-α mRNA expression levels were tested before and after anti-SREC-Ⅰ treatment.

Results: SREC-Ⅰ expressed in normal and A fumigatus treated HCECs and human corneal epithelium. In vitro experiment showed that SREC-Ⅰ mRNA and protein levels were significantly increased after A fumigatus stimulation. SREC-Ⅰ small interfering RNA treatment inhibited the expressions of LOX-1, IL-1β, and TNF-α in HCECs. The expressions of CLCX1, LOX-1, IL-1β, and TNF-α were elevated in mice with A fumigatus keratitis, which could be decreased by SREC-Ⅰ-neutralizing antibody treatment.

Conclusions: SREC-Ⅰ is a key mediator in inflammatory response induced by A fumigatus keratitis. SREC-Ⅰ blockade could be a potential therapeutic approach for FK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspergillosis / genetics*
  • Aspergillosis / immunology
  • Aspergillosis / microbiology
  • Aspergillus fumigatus / isolation & purification*
  • Blotting, Western
  • Cells, Cultured
  • Eye Infections, Fungal / genetics*
  • Eye Infections, Fungal / immunology
  • Eye Infections, Fungal / microbiology
  • Female
  • Gene Expression Regulation / genetics*
  • Humans
  • Immunity, Innate / genetics*
  • Keratitis / genetics*
  • Keratitis / immunology
  • Keratitis / microbiology
  • Male
  • Middle Aged
  • RNA, Messenger / genetics*
  • Scavenger Receptors, Class F / biosynthesis
  • Scavenger Receptors, Class F / genetics*

Substances

  • RNA, Messenger
  • SCARF1 protein, human
  • Scavenger Receptors, Class F