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Switched phenotypes of macrophages during the different stages of Schistosoma japonicum infection influenced the subsequent trends of immune responses
Journal of Microbiology, Immunology and Infection ( IF 4.5 ) Pub Date : 2021-07-17 , DOI: 10.1016/j.jmii.2021.06.005
Chen-Hsun Ho , Chia-Hsiung Cheng , Tzu-Wen Huang , Shih-Yi Peng , Kin-Mu Lee , Po-Ching Cheng

Background

Macrophages play crucial roles in immune responses during the course of schistosomal infections.

Methods

We currently investigated influence of immunocompetent changes in macrophages via microarray-based analysis, mRNA expression analysis, detection of serum cytokines, and subsequent evaluation of the immune phenotypes following the differentiation of infection-induced lymphocytes in a unique T1/T2 double-transgenic mouse model.

Results

The gradual upregulation of genes encoding YM1, YM2, and interleukin (IL)-4/IL-13 receptors in infected mice indicated the role of type 2 alternatively activated macrophages (M2, AAMφs) in immune responses after Schistosoma japonicum egg production. FACS analysis showed that surface markers MHC class II (IA/IE) and CD8α+ of the macrophages also exhibited a dramatic change at the various time points before and after egg-production. The transgenic mouse experiments further demonstrated that the shifting of macrophage phenotypes influenced the percentage of helper T (Th)-2 cells, which was observed to be higher than that of Th1 cells, which increased only at 3 and 5 weeks post-infection. The differentiation of effector B cells showed a similar but more significant trend toward type-2 immunity.

Conclusion

These results suggest that the infection of mice with S. japonicum resulted in a final Th2- and Be2-skewed immune response. This may be due to phenotypic changes in the macrophages. The influence of alternatively activated macrophages was also activated by S. japonicum egg production. This study elucidated the existence of variations in immune mechanisms at the schistosome infection stages.



中文翻译:

日本血吸虫感染不同阶段巨噬细胞表型转换影响后续免疫反应趋势

背景

在血吸虫感染过程中,巨噬细胞在免疫反应中起关键作用。

方法

我们目前通过基于微阵列的分析、mRNA 表达分析、血清细胞因子的检测以及在独特的 T1/T2 双转基因小鼠模型中感染诱导的淋巴细胞分化后免疫表型的后续评估,研究了巨噬细胞免疫活性变化的影响。 .

结果

感染小鼠中编码 YM1、YM2 和白细胞介素 (IL)-4/IL-13 受体的基因逐渐上调表明 2 型交替活化巨噬细胞 (M2, AAMφs) 在日本血吸虫产卵后的免疫反应中的作用。FACS 分析表明,表面标志物 MHC II 类 (IA/IE) 和 CD8α +巨噬细胞在产卵前后的不同时间点也表现出显着的变化。转基因小鼠实验进一步表明,巨噬细胞表型的变化影响了辅助 T (Th)-2 细胞的百分比,观察到辅助 T (Th)-2 细胞的百分比高于 Th1 细胞,后者仅在感染后 3 周和 5 周时增加。效应 B 细胞的分化表现出类似但更显着的 2 型免疫趋势。

结论

这些结果表明,用日本血吸虫感染小鼠会导致最终的 Th2 和 Be2 倾斜免疫反应。这可能是由于巨噬细胞的表型变化。交替激活的巨噬细胞的影响也被S. japonicum产卵激活。本研究阐明了在血吸虫感染阶段免疫机制存在变异。

更新日期:2021-07-17
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