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Aspergillus fumigatus-Stimulated Human Corneal Epithelial Cells Induce Pyroptosis of THP-1 Macrophages by Secreting TSLP

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Abstract

Fungal keratitis (FK) is a keratopathy caused by pathogenic fungal infection. The aim of this work is to explore the role of thymic stromal lymphopoietin (TSLP) in FK. Human corneal epithelial cells (HCECs) were treated with Aspergillus fumigatus hyphae, and we found that TSLP was highly expressed and secreted in the hyphae-treated HCECs. Hyphae-treated HCECs or TSLP treatment enhanced the expression of caspase-1 P20, GSDMD-N (p30), IL-1β, and IL-18 in the human THP-1 macrophages. The influence conferred by hyphae-treated HCECs or TSLP treatment was rescued by TSLP neutralizing antibody or VX-765 (caspase-1 inhibitor) treatment. Moreover, TSLP treatment promoted the expression of NLRP3, ASC, caspase-1 P20, GSDMD-N (p30), IL-1β, and IL-18 in the THP-1 macrophages, which was abolished by NLRP3 knockdown. Furthermore, TSLPR silencing suppressed the expression of NLRP3, ASC, caspase-1 P20, GSDMD-N (p30), IL-1β, and IL-18 in the TSLP-treated THP-1 macrophages. In conclusion, our article confirms that Aspergillus fumigatus-stimulated HCECs induce pyroptosis of THP-1 macrophages by secreting TSLP. TSLP/TSLPR induces caspase-1-dependent pyroptosis through activation of NLRP3 inflammasome. Thus, our work suggests that TSLP may be a potential target for FK treatment.

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Availability of Data and Material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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References

  1. Mahmoudi, S., A. Masoomi, K. Ahmadikia, S.A. Tabatabaei, M. Soleimani, S. Rezaie, H. Ghahvechian, and A. Banafsheafshan. 2018. Fungal keratitis: an overview of clinical and laboratory aspects. Mycoses 61 (12): 916–930. https://doi.org/10.1111/myc.12822.

    Article  PubMed  Google Scholar 

  2. Niu, L., X. Liu, Z. Ma, Y. Yin, L. Sun, L. Yang, and Y. Zheng. 2020. Fungal keratitis: pathogenesis, diagnosis and prevention. Microbial Pathogenesis 138: 103802. https://doi.org/10.1016/j.micpath.2019.103802.

    Article  PubMed  Google Scholar 

  3. Sharma, P., N. Sharma, P. Mishra, J. Joseph, D.K. Mishra, P. Garg, and S. Roy. 2019. Differential expression of antimicrobial peptides in Streptococcus pneumoniae keratitis and STAT3-dependent expression of LL-37 by Streptococcus pneumoniae in human corneal epithelial cells. Pathogens 8 (1). https://doi.org/10.3390/pathogens8010031.

  4. Sohn, H.J., G.E. Seo, J.H. Lee, A.J. Ham, Y.H. Oh, H. Kang, and H.J. Shin. 2019. Cytopathic change and inflammatory response of human corneal epithelial cells induced by Acanthamoeba castellanii Trophozoites and cysts. The Korean Journal of Parasitology 57 (3): 217–223. https://doi.org/10.3347/kjp.2019.57.3.217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Varricchi, G., A. Pecoraro, G. Marone, G. Criscuolo, G. Spadaro, A. Genovese, and G. Marone. 2018. Thymic stromal Lymphopoietin isoforms, inflammatory disorders, and cancer. Frontiers in Immunology 9: 1595. https://doi.org/10.3389/fimmu.2018.01595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ma, P., F. Bian, Z. Wang, X. Zheng, S. Chotikavanich, S.C. Pflugfelder, and D.Q. Li. 2009. Human corneal epithelium-derived thymic stromal lymphopoietin links the innate and adaptive immune responses via TLRs and Th2 cytokines. Investigative Ophthalmology & Visual Science 50 (6): 2702–2709. https://doi.org/10.1167/iovs.08-3074.

    Article  Google Scholar 

  7. Ren, X., L. Wang, and X. Wu. 2016. A potential link between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFκB-p65 in human corneal epithelial cells for Aspergillus fumigatus tolerance. Molecular Immunology 71: 98–106. https://doi.org/10.1016/j.molimm.2015.12.014.

    Article  CAS  PubMed  Google Scholar 

  8. Dai, C., J. Wu, C. Chen, and X. Wu. 2019. Interactions of thymic stromal lymphopoietin with TLR2 and TLR4 regulate anti-fungal innate immunity in Aspergillus fumigatus-induced corneal infection. Experimental Eye Research 182: 19–29. https://doi.org/10.1016/j.exer.2019.02.020.

    Article  CAS  PubMed  Google Scholar 

  9. Wang, L., L. Wang, and X. Wu. 2016. Aspergillus fumigatus promotes T helper type 2 responses through thymic stromal lymphopoietin production by human corneal epithelial cells. Clinical & Experimental Ophthalmology 44 (6): 492–501. https://doi.org/10.1111/ceo.12706.

    Article  Google Scholar 

  10. Sun, L., C. Chen, J. Wu, C. Dai, and X. Wu. 2018. TSLP-activated dendritic cells induce T helper type 2 inflammation in Aspergillus fumigatus keratitis. Experimental Eye Research 171: 120–130. https://doi.org/10.1016/j.exer.2018.03.014.

    Article  CAS  PubMed  Google Scholar 

  11. Cui, X., N. Gao, R. Me, J. Xu, and F.X. Yu. 2018. TSLP protects corneas from Pseudomonas aeruginosa infection by regulating dendritic cells and IL-23-IL-17 pathway. Investigative Ophthalmology & Visual Science 59 (10): 4228–4237. https://doi.org/10.1167/iovs.18-24672.

    Article  CAS  Google Scholar 

  12. Hu, J., Y. Hu, S. Chen, C. Dong, J. Zhang, Y. Li, J. Yang, X. Han, X. Zhu, and G. Xu. 2014. Role of activated macrophages in experimental Fusarium solani keratitis. Experimental Eye Research 129: 57–65. https://doi.org/10.1016/j.exer.2014.10.014.

    Article  CAS  PubMed  Google Scholar 

  13. Lin, J., K. He, G. Zhao, C. Li, L. Hu, G. Zhu, Y. Niu, and G. Hao. 2017. Mincle inhibits neutrophils and macrophages apoptosis in A. fumigatus keratitis. International Immunopharmacology 52: 101–109. https://doi.org/10.1016/j.intimp.2017.08.006.

    Article  CAS  PubMed  Google Scholar 

  14. Man, S.M., R. Karki, and T.D. Kanneganti. 2017. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunological Reviews 277 (1): 61–75. https://doi.org/10.1111/imr.12534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Qu, W., Y. Wang, Y. Wu, Y. Liu, K. Chen, X. Liu, Z. Zou, X. Huang, and M. Wu. 2018. Pseudomonas aeruginosa triggering receptors expressed on myeloid cells 2 promotes corneal resistance against by inhibiting caspase-1-dependent pyroptosis. Frontiers in Immunology 9: 1121. https://doi.org/10.3389/fimmu.2018.01121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Soumelis, V., and Y.J. Liu. 2020. The discovery of human TSLP as a critical epithelial cytokine in type 2 immunity and allergic disease. Nature Immunology. https://doi.org/10.1038/s41590-020-0720-7.

  17. Huang, R., W. Mao, G. Wang, J. Ding, Y. Sun, G. Gao, P. Dong, and Z. Sun. 2020. Synergistic relationship between TSLP and IL-33/ST2 signaling pathways in allergic rhinitis and the effects of hypoxia. International forum of allergy & rhinology 10 (4): 511–520. https://doi.org/10.1002/alr.22504.

    Article  Google Scholar 

  18. Lai, J.F., L.J. Thompson, and S.F. Ziegler. 2020. TSLP drives acute T2-cell differentiation in lungs. The Journal of allergy and clinical immunology. https://doi.org/10.1016/j.jaci.2020.03.032.

  19. Li, S., Z. Yi, M. Deng, M.J. Scott, C. Yang, W. Li, Z. Lei, N.M. Santerre, P. Loughran, and T.R. Billiar. 2019. TSLP protects against liver I/R injury via activation of the PI3K/Akt pathway. JCI insight 4 (22). https://doi.org/10.1172/jci.insight.129013.

  20. Kato, T., H. Kouzaki, K. Matsumoto, J. Hosoi, and T. Shimizu. 2017. The effect of calprotectin on TSLP and IL-25 production from airway epithelial cells. Allergology international : official journal of the Japanese Society of Allergology 66 (2): 281–289. https://doi.org/10.1016/j.alit.2016.06.011.

    Article  CAS  Google Scholar 

  21. Mariathasan, S., D.S. Weiss, K. Newton, J. McBride, K. O'Rourke, M. Roose-Girma, W.P. Lee, Y. Weinrauch, D.M. Monack, and V.M. Dixit. 2006. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440 (7081): 228–232. https://doi.org/10.1038/nature04515.

    Article  CAS  PubMed  Google Scholar 

  22. Faustin, B., L. Lartigue, J.M. Bruey, F. Luciano, E. Sergienko, B. Bailly-Maitre, N. Volkmann, D. Hanein, I. Rouiller, and J.C. Reed. 2007. Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Molecular Cell 25 (5): 713–724. https://doi.org/10.1016/j.molcel.2007.01.032.

    Article  CAS  PubMed  Google Scholar 

  23. Zhaolin, Z., L. Guohua, W. Shiyuan, and W. Zuo. 2019. Role of pyroptosis in cardiovascular disease. Cell Proliferation 52 (2): e12563. https://doi.org/10.1111/cpr.12563.

    Article  PubMed  Google Scholar 

  24. Yu, X., Y. Peng, H. Liang, K. Fu, Z. Zhao, C. Xie, L. Zhou, and K. Zhang. 2018. TSLP/TSLPR promote angiogenesis following ischemic stroke via activation of the PI3K/AKT pathway. Molecular Medicine Reports 17 (2): 3411–3417. https://doi.org/10.3892/mmr.2017.8217.

    Article  CAS  PubMed  Google Scholar 

  25. Deng, R., X. Chen, Y. Zhang, F. Bian, N. Gao, J. Hu, C. Wang, R.G. de Souza, F. Lu, S.C. Pflugfelder, and D.Q. Li. 2019. Short ragweed pollen promotes M2 macrophage polarization via TSLP/TSLPR/OX40L signaling in allergic inflammation. Mucosal Immunology 12 (5): 1141–1149. https://doi.org/10.1038/s41385-019-0187-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Dong, J., J. Dong, J. Lin, B. Wang, S. He, C. Wu, K.K. Kushwaha, N. Mohabeer, Y. Su, H. Fang, K. Huang, and D. Li. 2015. Inflammatory cytokine TSLP stimulates platelet secretion and potentiates platelet aggregation via a TSLPR-dependent PI3K/Akt signaling pathway. Cellular Physiology and Biochemistry 35 (1): 160–174. https://doi.org/10.1159/000369684.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was approved by the Foreign Science and Technology Cooperation Project of Science and Technology Department in Anhui Province, China (Grant No.201904b11020042); the Natural Science Foundation of Anhui (1908085MH253).

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Authors and Affiliations

  1. Department of ophthalmology, The First Affiliated Hospital of USTC, Division of life sciences and medicine, University of Science and Technology of China, No. 17, Lujiang Road, Hefei, 230001, Anhui, China

    Qingshan Ji, Lisong Wang, Jiajia Liu, Yali Wu, Huayi Lv, Yuechun Wen & Lei Shi

  2. Dr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Kirrberger Strasse 100 Geb. 22, 66424, Homburg, Saarland, Germany

    Lei Shi & Nóra Szentmáry

  3. Biophysics Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, Kirrberger Strasse 100 Geb. 48, 66421, Homburg, Saarland, Germany

    Bin Qu

  4. Department of ophthalmology, Semmelweis University, Budapest, Hungary

    Nóra Szentmáry

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  1. Qingshan Ji
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  2. Lisong Wang
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Contributions

Q. Ji, L. Wang designed the study; all authors conducted the experiments and analyzed the data; Q. Ji drafted the paper; L. Shi reviewed the manuscript. All authors approved the paper.

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Correspondence to Lei Shi.

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Qingshan Ji and Lisong Wang are co-first authors

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Ji, Q., Wang, L., Liu, J. et al. Aspergillus fumigatus-Stimulated Human Corneal Epithelial Cells Induce Pyroptosis of THP-1 Macrophages by Secreting TSLP. Inflammation 44, 682–692 (2021). https://doi.org/10.1007/s10753-020-01367-x

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  • DOI: https://doi.org/10.1007/s10753-020-01367-x

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