Open Access

Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses through M2 polarization of macrophages

  • Authors:
    • Jia‑Jie Chen
    • Yong‑Shen He
    • Xiao‑Jun Zhong
    • Ze‑Lang Cai
    • Yan‑Si Lyu
    • Zhen‑Fu Zhao
    • Kunmei Ji
  • View Affiliations

  • Published online on: May 21, 2020     https://doi.org/10.3892/ijmm.2020.4613
  • Pages: 718-728
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic immunological response to Aspergillus fumigatus (Af) exposure, which induces a strong T helper 2 (Th2) response via mechanisms that have yet to be elucidated. The aim of the present study was to investigate the hypothesis that T2 ribonuclease from Af (Af RNASET2) induces M2‑type macrophage polarization to produce a T helper 2 (Th2) immune response. Recombinant Af RNASET2 (rAf RNASET2) was expressed and purified in a prokaryotic pET system and BALB/c mice were immunized with rAf RNASET2 for in vivo analyses. Expression levels of M2 polarization factors were evaluated in RAW264.7 macrophages treated with rAf RNASET2 in vitro using flow cytometry, reverse transcription‑quantitative PCR, and western blot analysis. The results predicted that the mature Af RNASET2 protein (382 amino acids; GenBank no. MN593022) contained two conserved amino acid sequence (CAS) domains, termed CAS‑1 and CAS‑2, which are also characteristic of the RNASET2 family proteins. The protein expression levels of the Th2‑related cytokines interleukin (IL)‑4, IL‑10, and IL‑13 were upregulated in mice immunized with rAf RNASET2. RAW264.7 macrophages treated with rAf RNASET2 showed increased mRNA expression levels of M2 factors [arginase 1, Il‑10, and Il‑13]; however, there was no difference in cells treated with rAf RNASET2 that had been inactivated with a ribonuclease inhibitor (RNasin). The protein expression levels of IL‑10 in macrophage culture supernatant were also increased following stimulation with rAf RNASET2. In addition, rAf RNASET2 upregulated the expression of phosphorylated mitogen activated protein kinases (MAPKs) in RAW264.7 cells, whereas MAPK inhibitors attenuated rAf RNASET2‑induced IL‑10 expression in RAW264.7 cells. In conclusion, the present study reveals that high rAf RNASET2 activity is required for rAf RNASET2‑induced M2 polarization of macrophages and suggests an important immune regulatory role for Af RNASET2 in ABPA pathogenesis.
View Figures
View References

Related Articles

Journal Cover

August-2020
Volume 46 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos
Chen J, He Y, Zhong X, Cai Z, Lyu Y, Zhao Z and Ji K: Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses through M2 polarization of macrophages. Int J Mol Med 46: 718-728, 2020
APA
Chen, J., He, Y., Zhong, X., Cai, Z., Lyu, Y., Zhao, Z., & Ji, K. (2020). Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses through M2 polarization of macrophages. International Journal of Molecular Medicine, 46, 718-728. https://doi.org/10.3892/ijmm.2020.4613
MLA
Chen, J., He, Y., Zhong, X., Cai, Z., Lyu, Y., Zhao, Z., Ji, K."Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses through M2 polarization of macrophages". International Journal of Molecular Medicine 46.2 (2020): 718-728.
Chicago
Chen, J., He, Y., Zhong, X., Cai, Z., Lyu, Y., Zhao, Z., Ji, K."Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses through M2 polarization of macrophages". International Journal of Molecular Medicine 46, no. 2 (2020): 718-728. https://doi.org/10.3892/ijmm.2020.4613