Switched phenotypes of macrophages during the different stages of Schistosoma japonicum infection influenced the subsequent trends of immune responses

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.