Citation:Zhang L, Jiang N, Zhao GQ, Peng XD, Zhu GQ, Jiang W, Ma JJ. Expression and role of aryl hydrocarbon receptor in Aspergillus fumigatus keratitis. Int J Ophthalmol 2020;13(2):199-205,doi:10.18240/ijo.2020.02.01
Expression and role of aryl hydrocarbon receptor in Aspergillus fumigatus keratitis
Received:November 18, 2019  Revised:December 07, 2019
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DOI:10.18240/ijo.2020.02.01
Key Words:aryl hydrocarbon receptor  keratitis  Aspergillus fumigatus  innate immune response
Fund Project:Supported by the National Natural Science Foundation of China (No.81870632); the Youth National Natural Science Foundation of China (No.81700800; No.81800800); the Natural Science Foundation of Shandong Province (No.ZR2019BH004; No.ZR2017MH008; No.ZR2017BH025).
                    
AuthorInstitution
Li Zhang Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao , Shandong Province, China
Nan Jiang Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao , Shandong Province, China
Gui-Qiu Zhao Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao , Shandong Province, China
Xu-Dong Peng Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao , Shandong Province, China
Guo-Qiang Zhu Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao , Shandong Province, China
Wei Jiang Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao , Shandong Province, China
Jing-Jing Ma Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao , Shandong Province, China
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Abstract:
      AIM: To observe the expression and role of aryl hydrocarbon receptor (AhR) in the immune response of mouse cornea infected with Aspergillus fumigatus (A. fumigatus).

    METHODS: Murine models of A. fumigatus keratitis were established by scraping the central epithelium of mouse cornea, daubing A. fumigatus on the cornea and covering with a contact lens. The mice were randomly divided into the control group and the A. fumigatus-infected (A.F.) group for 1, 3 and 5d respectively, which corneas were daily monitored by a slit lamp microscope and the clinical scores were also recorded timely after infection. In this study, immunofluorescence staining was used to detect the expression and localization of AhR in mouse corneas, and the mRNA and protein of AhR were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. In addition, mouse peritoneal macrophages were stimulated by A. fumigatus with or without the pretreatment of AhR antagonist CH223191 and AhR agonist FICZ, and the tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10) and Arg-1 mRNA were detected by RT-PCR.

    RESULTS: According to the results of the slit light photography, it was clearly indicated that the corneal inflammation were the most severe and the clinical score became the highest as well on the 3rd day after the infection of A. fumigatus. Contrasted with the control group, the expression of AhR in the corneal epithelial cells infected with A. fumigatus was significantly increased detected by immunofluorescence staining. AhR mainly expressed in the nucleus and cytoplasm of corneal epithelial cells. Consistent with the transcriptional level of AhR mRNA, the expression level of AhR protein reached the peak on the 3rd day after infection which was detected by Western blot. Furthermore, RT-PCR showed that CH223191 up-regulated the expression of TNF-α and iNOS and down-regulated the expression of IL-10 and Arg-1 in peritoneal macrophages; inversely, FICZ reduced the expression of TNF-α and iNOS while elevated the expression of IL-10 and Arg-1.

    CONCLUSION: AhR is involved in the pathogenesis of A. fumigatus keratitis and induced immune protection in anti-A. fumigatus immune response by inhibiting M1 and increasing M2 phenotype macrophage-related inflammatory factors.

PMC FullText Html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013794/
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