Leukocyte Immunoglobulin-like Receptor A5 Deletion Aggravates the Pathogenesis of Pseudomonas aeruginosa Keratitis by Promoting Proinflammatory Cytokines

Cornea. 2023 May 1;42(5):607-614. doi: 10.1097/ICO.0000000000003205. Epub 2022 Dec 19.

Abstract

Purpose: The purpose of this study was to assess the role of leukocyte immunoglobulin-like receptor A5 (LILRA5) in regulating bacterial infection and corneal inflammation.

Methods: The human corneal tissue microarray data set GSE58291 from Gene Expression Omnibus was downloaded. Then, the differentially expressed genes, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis, and the immune infiltration analysis were conducted. We constructed the Pseudomonas aeruginosa ( P. aeruginosa ) keratitis mice model using wild-type and LILRA5-deficient mice. The results of the bioinformatics analysis were verified by the cell in vitro and animal in vivo experiments.

Results: This study revealed that LILRA5 is substantially expressed in human keratitis and regulates the immune response negatively. Neutrophils were identified as the core fraction of immune cells in keratitis. After P. aeruginosa infection, neutrophils lacking LILRA5 induced elevated levels of proinflammatory cytokines and toll-like receptor 4. LILRA5 deficiency exacerbated the severity of the infection and the production of proinflammatory cytokines in mice.

Conclusions: LILRA5 was discovered as an immunosuppressive regulator in P. aeruginosa keratitis, highlighting its significance in activated immune responses.

MeSH terms

  • Animals
  • Cornea / pathology
  • Cytokines / metabolism
  • Humans
  • Immunoglobulins / metabolism
  • Keratitis* / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa
  • Receptors, Immunologic* / genetics

Substances

  • Cytokines
  • Immunoglobulins
  • Receptors, Immunologic