Study on Differences in the Pathology, T Cell Subsets and Gene Expression in Susceptible and Non-Susceptible Hosts Infected with Schistosoma japonicum

Abstract

More than 40 kinds of mammals in China are known to be naturally infected with Schistosoma japonicum (S. japonicum); Microtus fortis (M. fortis), a species of vole, is the only mammal in which the schistosomes cannot mature or cause significant pathogenic changes. In the current study, we compared the differences in pathology by Hematoxylin-eosin staining and in changes in the T cell subsets with flow cytometry as well as gene expression using genome oligonucleotide microarrays in the lung and liver, before challenge and 10 days post-infection with schistosomes in a S. japonicum-susceptible mouse model of infection, a non-susceptible rat model and the non-permissive host, M. fortis. The results demonstrated that S. japonicum promoted a more intensive immune response and more pathological lesions in M. fortis and rats than in mice. Hematoxylin-eosin staining revealed that the immune effector cells involved were mainly eosinophilic granulocytes supplemented with heterophilic granulocytes and macrophages. The analysis of splenic T cell subsets showed that CD4+ T cell subsets and the CD4+/CD8+ ratio were increased, while the CD8+ T cell subsets decreased remarkably in rats; whereas the CD8+ T cell subsets were increased, but the CD4+/CD8+ ratio was decreased significantly in mice. The analysis of the pattern of gene expression suggested that some immune-associated genes and apoptosis-inducing genes up-regulated, while some development-associated genes were down-regulated in the infected M. fortis compared to the uninfected controls; the three different hosts have different response mechanisms to schistosome infection. The results of this study will be helpful for identifying the key molecules in the immune response to S. japonicum in M. fortis and for understanding more about the underlying mechanism of the response, as well as for elucidating the interaction between S. japonicum and its hosts.

Specific humoral response of hosts with variable schistosomiasis susceptibility

“…Knowledge of these antigens is not just important for the immunobiology of schistosomiasis but specifically could be exploited for the discovery and development of vaccines and diagnostics. The rat has long been used as a model of immunological resistance for both S. japonicum 7 , 8 , 18 , 59 and S. mansoni 10 , 11 , 15 , 60 infection. Consequently, we screened serum and tissue antibodies from the rat using a protein microarray.…”

“…Equivalent time points were collected for the control groups in both rat time courses. Similar to previous studies, 8 , 19 , 59 , 61 we used outbred rats to better model the host heterogeneity found in schistosome‐endemic animal and human populations. Blood was collected during the time course and at necropsy.…”

Changes in microRNA expression in response to Schistosoma japonicum infection

“…Schistosomes from different development stages or from different susceptible hosts show differences in the level of transcription and of translation of certain genes. These differences are significantly affected by their host's environment and the host's response to the parasite infection, but knowledge regarding the mechanisms of host‐pathogen interaction via noncoding RNAs is still limited.…”

Immunoproteomic analysis of Schistosoma japonicum schistosomulum proteins recognized by immunoglobulin G in the sera of susceptible and non-susceptible hosts

“…It is possible that M. fortis has a stronger immune response to the schistosomes during the early phases of infection, with more severe pathological lesions. Previous studies have also shown that humoral and/or cellular immunity play important roles in the restricted development of S. japonicum in M. fortis [12]. Normal sera were transferred from M. fortis into mice and the growth and development of schistosomes in these mice were affected [13].…”