Indoleamine 2,3-dioxygenase adjusts neutrophils recruitment and chemotaxis in Aspergillus fumigatus keratitis

Shu-Xuan Guo; Nan Jiang; Li Zhang; Wei Jiang; Jing-Jing Ma

doi:10.18240/ijo.2022.03.02

Indoleamine 2,3-dioxygenase adjusts neutrophils recruitment and chemotaxis in Aspergillus fumigatus keratitis

Int J Ophthalmol. 2022 Mar 18;15(3):380-387. doi: 10.18240/ijo.2022.03.02. eCollection 2022.

Authors

Shu-Xuan Guo¹, Nan Jiang¹, Li Zhang¹, Wei Jiang¹, Jing-Jing Ma¹

Affiliation

¹ Qingdao University, Qingdao 266003, Shandong Province, China.

Abstract

Aim: To explore the effect of indoleamine 2,3-dioxygenase (IDO) on recruitment and chemotaxis function of neutrophils in Aspergillus fumigatus (A. fumigatus) keratitis.

Methods: C57BL/6 mice models of A. fumigatus keratitis were established by inoculating hyphae of A. fumigatus evenly on the corneas. The clinical scores and inflammatory cytokines expression were measured respectively on the 1^st, 3^rd, 5^th day after infection. The 1-MT (1 mg/mL) was administered by gavage to exert an inhibitory effect on IDO during infection. The mice were divided into control group, 1-MT group, A. fumigatus (A.F.) group, and 1-MT+A.F. groups. The corneas were monitored by slit lamp microscopy, and recorded disease scores in 3d after infection. Myeloperoxidase (MPO) assay was done to evaluate the neutrophils infiltration. Immunofluorescence staining was used to detect the recruitment of neutrophils in murine corneas. The mRNA of inflammatory cytokines was measured with reverse transcription-polymerase chain reaction (RT-PCR).

Results: The corneal inflammation and the clinical score reached the peak on the 3^rd day after the corneal infection. The mRNA of inflammatory cytokines of the A.F. group reached the highest on the 3^rd day after the infection accordingly. Meanwhile, the results of slit light photography indicated that inhibitors of IDO made inflammation more serious contrasted with the A.F. group on the 3^rd day. Besides, imunofluorescence staining and MPO indicated that 1-MT enhanced the recruitment, infiltration and chemotaxis of neutrophils obviously in contrast to the A.F. group. RT-PCR indicated that 1-MT increased the expression of CXCL-1, ICAM-1, IL-1β, and IL-8 significantly.

Conclusion: IDO participates in the pathogenesis of A. fumigatus keratitis and plays an important role in inducing immune protection by inhibiting neutrophils-related inflammatory reaction and suppressing recruitment and chemotaxis of the neutrophils.

Keywords: Aspergillus fumigatus; indoleamine 2,3-dioxygenase; innate immune; keratitis; neutrophils.

International Journal of Ophthalmology Press.