2. Academic Validation
  3. Candidalysin amplifies the immune inflammatory response in Candida albicans keratitis through the TREM-1/DAP12 pathway

Candidalysin amplifies the immune inflammatory response in Candida albicans keratitis through the TREM-1/DAP12 pathway

  • Int Immunopharmacol. 2023 Apr 21;119:110195. doi: 10.1016/j.intimp.2023.110195.
Liting Hu 1,  Guitao Bai 2,  Qiang Xu 1,  Guiqiu Zhao 1,  Nan Jiang 1,  Hua Yao 1,  Xueqing Liu 1,  Zhaodong Du 3
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China.
  • 2 Department of Ophthalmology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China; Department of Ophthalmology, Zigong First People's Hospital, 42 Shang Yihao Branch Road, ZiGong 643000, China.
  • 3 Department of Ophthalmology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China. Electronic address: [email protected].
PMID: 37087869 DOI: 10.1016/j.intimp.2023.110195
Abstract

Candidalysin is a Fungal peptide toxin secreted by Candida albicans hyphae during invasion into epithelial cells. In Candida albicans-infected mucosa, candidalysin causes epithelial cell damage and activates downstream inflammatory responses, especially the release of inflammatory cytokines. However, the role of candidalysin in Candida albicans corneal keratitis remains unexplored. Moreover, it remains unclear whether candidalysin regulates the inflammatory response through the TREM-1/DAP12 pathway in Candida albicans corneal keratitis. In this study, we determined the expression pattern of TREM-1 in a mouse model of Candida albicans corneal keratitis and investigated the molecular mechanism underlying the inflammatory response regulation by candidalysin. The corneal keratitis model was established in C57BL/6 mice. In the GF9 group, mice were pretreated and then treated with the TREM-1 inhibitor GF9; in the candidalysin group, mice were treated with peptide candidalysin; and in the PD98059 group, mice were pretreated with the ERK Inhibitor PD98059. Slit-lamp photography, clinical scoring, PCR, western blotting and immunofluorescence assay were performed to observe disease response and GF9 therapeutic efficacy. Pretreatment with candidalysin or PD98059 was performed before Candida albicans Infection. GF9 treatment reduced the expression of TREM-1 and cytokines in the infected mouse cornea, whereas candidalysin treatment increased the expression of TREM-1, p-ERK, and cytokines, and this increase was inhibited by GF9. The candidalysin-induced increment of TREM-1, p-ERK, and cytokines was inhibited by PD98059 pretreatment. These data suggest that candidalysin can initiate inflammatory response in Candida albicans corneal keratitis through the TREM-1/DAP12 pathway and can regulate cytokine expression by enhancing ERK phosphorylation.

Keywords

Candida albicans; Extracellular signal-regulated kinase; Mouse cornea; Triggering receptor expressed on myeloid cells.

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